FASENRA™ (benralizumab)

benralizumab

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Highlights of Prescribing Information

<?xml version="1.0" encoding="UTF-8"?><title>These highlights do not include all the information needed to use FASENRA<sup>®</sup> safely and effectively. See full prescribing information for FASENRA.<br/>FASENRA (benralizumab) injection, for subcutaneous use<br/>Initial U.S. Approval: 2017</title>

SPL product data elements section
RECENT MAJOR CHANGES SECTION
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
13 NONCLINICAL TOXICOLOGY
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
SPL PATIENT PACKAGE INSERT SECTION
INSTRUCTIONS FOR USE SECTION
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
Package/Label Display Panel

SPL product data elements section

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<?xml version="1.0" encoding="UTF-8"?><section ID="ID_3be61cde-82ca-4749-93ab-9df3028f0766"> <id root="cb2de442-1abe-42e0-b11c-20a98b3aa358"/> <code code="43683-2" codeSystem="2.16.840.1.113883.6.1" displayName="RECENT MAJOR CHANGES SECTION"/> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph/> <paragraph>Indications and Usage (<linkHtml href="#ID_a6c6cb8e-80f1-4db7-9473-78eef7bc41c1">1</linkHtml>) 09/2024</paragraph> <paragraph>Dosage and Administration (<linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">2.1</linkHtml>, <linkHtml href="#ID_5a6bd955-ba4e-4627-b03a-e95c9b809f12">2.3</linkHtml>, <linkHtml href="#ID_f2b53792-eabe-4ce2-9694-f55e1645348c">2.4</linkHtml>) 04/2024</paragraph> <paragraph>Dosage and Administration, EGPA (<linkHtml href="#ID_83f69064-d965-4491-b431-1cc77b3ffb45">2.2</linkHtml>) 09/2024</paragraph> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_a6c6cb8e-80f1-4db7-9473-78eef7bc41c1"> <id root="c7efcdac-3ae5-4e2f-b477-aef158fd24ae"/> <code code="34067-9" codeSystem="2.16.840.1.113883.6.1" displayName="INDICATIONS & USAGE SECTION"/> <title>1 INDICATIONS AND USAGE </title> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph>FASENRA is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for:</paragraph> <list listType="unordered"> <item> <caption>•</caption>add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype. <linkHtml href="#ID_3be61cde-82ca-4749-93ab-9df3028f0766">(1.1)</linkHtml> </item> <item> <caption>•</caption>treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). (1.2)</item> </list> <paragraph> </paragraph> <paragraph> <content styleCode="underline">Limitations of Use:</content> </paragraph> <paragraph>Not for relief of acute bronchospasm or status asthmaticus. <linkHtml href="#ID_3be61cde-82ca-4749-93ab-9df3028f0766">(1.1)</linkHtml> </paragraph> </text> </highlight> </excerpt> <component> <section ID="ID_0c6c7edc-324f-4c7b-8320-ed18874aeead"> <id root="83631138-66b3-44b7-a5a7-4ddc6d2bf7e7"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>1.1 Asthma </title> <text> <paragraph> <content styleCode="xmChange">FASENRA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype <content styleCode="italics">[see <linkHtml href="#ID_9d42e499-4c01-461c-aa86-a61725586176">Use in Specific Populations (8.4)</linkHtml>, <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14.1)</linkHtml>]</content>.</content> </paragraph> <paragraph>Limitations of Use:</paragraph> <list listType="unordered"> <item> <caption>•</caption>FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus.</item> </list> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_144dbff4-2117-4c89-bd7a-c9483c8befa9"> <id root="1efaf9e0-2f1e-4b4d-9cf4-92c4fec2141a"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>1.2 Eosinophilic Granulomatosis with Polyangiitis </title> <text> <paragraph> <content styleCode="xmChange">FASENRA is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).</content> </paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_702ea00c-8117-4e2d-b196-94ec1e6c7c3d"> <id root="76b5e6a0-09c4-441a-9e31-37b69985f5c4"/> <code code="34068-7" codeSystem="2.16.840.1.113883.6.1" displayName="DOSAGE & ADMINISTRATION SECTION"/> <title>2 DOSAGE AND ADMINISTRATION </title> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph>Administer by subcutaneous injection. (<linkHtml href="#ID_5a6bd955-ba4e-4627-b03a-e95c9b809f12">2.3</linkHtml>)</paragraph> <paragraph> <content styleCode="underline">Asthma</content> </paragraph> <paragraph> <content styleCode="italics">Adult and Adolescent Patients 12 Years of Age and Older: </content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. (<linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">2.1</linkHtml>)</item> </list> <paragraph> <content styleCode="italics">Pediatric Patients 6 Years to 11 Years of Age:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="italics">Weighing Less Than 35 kg</content>: the recommended dosage is 10 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. (<linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">2.1</linkHtml>)</item> <item> <caption>•</caption> <content styleCode="italics">Weighing 35 kg or More</content>: the recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. (<linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">2.1</linkHtml>)</item> </list> <paragraph> <content styleCode="underline">EGPA</content> </paragraph> <paragraph>Recommended dosage is 30 mg every 4 weeks. (2.2)</paragraph> <paragraph>See full prescribing information for administration instructions of FASENRA prefilled syringe and FASENRA PEN. (<linkHtml href="#ID_79100255-b8ab-410a-9f71-f1ae3bbfb0b9">2.4</linkHtml>, 2.5)</paragraph> </text> </highlight> </excerpt> <component> <section ID="ID_07b5e868-a789-491f-bed0-3726140b03c4"> <id root="d77301ab-067d-45ab-9227-950c99b5171a"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.1 Recommended Dosage for Asthma </title> <text> <paragraph> <content styleCode="xmChange"> <content styleCode="underline">Adult and Adolescent Patients 12 Years of Age and Older</content> </content> </paragraph> <paragraph> <content styleCode="xmChange">The recommended dosage of FASENRA is 30 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.</content> </paragraph> <paragraph> <content styleCode="xmChange"> <content styleCode="underline">Pediatric Patients 6 to 11 Years of Age</content> </content> </paragraph> <paragraph> <content styleCode="xmChange">The recommended dosage of FASENRA for pediatric patients 6 to 11 years of age is based on body weight as provided in <content styleCode="bold">Table 1</content>.</content> </paragraph> <table width="100%"> <caption>Table 1. Recommended Dosage of FASENRA in Pediatric Patients 6 to 11 Years of Age with Asthma</caption> <col width="20%"/> <col width="80%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Body weight</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Recommended Dosage</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Less than 35 kg</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>10 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>35 kg or more</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>30 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_83f69064-d965-4491-b431-1cc77b3ffb45"> <id root="d980b5b4-49de-41ba-9674-243f2f650ffa"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.2 Recommended Dosage for EGPA </title> <text> <paragraph> <content styleCode="xmChange">The recommended dosage of FASENRA is 30 mg (one injection) administered once every 4 weeks by subcutaneous injection</content>.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_5a6bd955-ba4e-4627-b03a-e95c9b809f12"> <id root="236987db-2295-4ec9-8566-25b64503b623"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.3 General Administration Instructions </title> <text> <paragraph> <content styleCode="xmChange">FASENRA is for subcutaneous use only.</content> </paragraph> <paragraph> <content styleCode="xmChange">FASENRA is intended for use under the guidance of a healthcare provider. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended <content styleCode="italics">[see <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">Warnings and Precautions (5.1)</linkHtml>]</content>.</content> </paragraph> <paragraph> <content styleCode="xmChange">Administer FASENRA into the thigh or abdomen. The upper arm can also be used if a healthcare provider or caregiver administers the injection. Prior to administration, warm FASENRA by leaving carton at room temperature for about 30 minutes. Visually inspect FASENRA for particulate matter and discoloration prior to administration. FASENRA is clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles. Do not use FASENRA if the liquid is cloudy, discolored, or if it contains large particles or foreign particulate matter.</content> </paragraph> <paragraph> <content styleCode="xmChange"> <content styleCode="underline">Prefilled Syringe</content> </content> </paragraph> <paragraph> <content styleCode="xmChange">The prefilled syringe is for administration by a healthcare provider.</content> </paragraph> <paragraph> <content styleCode="xmChange"> <content styleCode="underline">Autoinjector (FASENRA PEN™)</content> </content> </paragraph> <paragraph> <content styleCode="xmChange">FASENRA PEN is intended for administration by patients/caregivers. Patients/caregivers may inject after proper training in subcutaneous injection technique, and after the healthcare provider determines it is appropriate.</content> </paragraph> <paragraph> <content styleCode="xmChange">In asthma patients aged 6 to 11 years weighing 35 kg or more, FASENRA PEN should only be administered by a caregiver or healthcare provider.</content> </paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_f2b53792-eabe-4ce2-9694-f55e1645348c"> <id root="87803712-108c-4147-ac1f-4483d788eb10"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.4 Instructions for Administration of FASENRA Prefilled Syringe (Healthcare Providers) </title> <text> <list listType="ordered"> <item> <caption> </caption> <content styleCode="xmChange"> <content styleCode="bold">Figure 1 FASENRA Prefilled Syringes</content> </content> </item> </list> <content styleCode="xmChange"> <renderMultiMedia ID="id-455330073" referencedObject="ID_18259d26-043f-4e87-8e3c-3b0f29a353e7"/> </content> <paragraph> <content styleCode="underline">Prefilled Syringe Components</content> </paragraph> <renderMultiMedia ID="id-1145972171" referencedObject="C742B361-4234-44D7-8BBA-115C27F5E181"/> <paragraph>To prepare FASENRA prefilled syringe for subcutaneous administration, carefully read and adhere to these instructions for use. FASENRA is available in a 10 mg and a 30 mg prefilled syringe. Check the labels on the FASENRA carton and prefilled syringe to ensure the correct 10 mg or 30 mg product is being used (Figure 1). Refer to Figure 1 to identify the prefilled syringe components for use in the administration steps.</paragraph> <paragraph> <content styleCode="bold">Do not touch the needle guard activation clips </content>to prevent premature activation of the needle safety guard.</paragraph> <table width="97.92%"> <col width="4%"/> <col width="28%"/> <col width="68%"/> <tbody> <tr styleCode="Toprule"> <td valign="top"> <paragraph>1</paragraph> </td> <td colspan="2" valign="top"> <paragraph> <content styleCode="bold">Grasp the syringe body</content>, not the plunger, to remove prefilled syringe from the tray. Check the expiration date on the syringe. The syringe may contain small air bubbles; this is normal. <content styleCode="bold">Do not</content> expel the air bubbles prior to administration.</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>2</paragraph> </td> <td valign="top"> <renderMultiMedia ID="id2109077253" referencedObject="C6E3C808-FE0A-4AE0-9C65-0B29427F16C2"/> </td> <td valign="middle"> <paragraph>Do not remove needle cover until ready to inject. Hold the syringe body and remove the needle cover by pulling straight off. Do not hold the plunger or plunger head while removing the needle cover or the plunger may move. If the prefilled syringe is damaged or contaminated (for example, dropped without needle cover in place), discard and use a new prefilled syringe.<br/> </paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>3</paragraph> </td> <td valign="top"> <renderMultiMedia ID="id-305479760" referencedObject="D7DDBF26-3C0F-4BFC-B678-C1BE0EBB9202"/> </td> <td valign="middle"> <paragraph>Gently pinch the skin and insert the needle at the recommended injection site (i.e., upper arm, thigh, or abdomen).</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>4</paragraph> </td> <td valign="top"> <renderMultiMedia ID="id750782175" referencedObject="ID_7459ea9e-f5c4-4f96-8cf8-e4bd555b3b70"/> </td> <td valign="middle"> <paragraph>Inject all of the medication by pushing in the plunger all the way until the plunger head is <content styleCode="bold">completely between</content> the needle guard activation clips. <content styleCode="bold">This is necessary to activate the needle guard.</content> </paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>5</paragraph> </td> <td valign="top"> <renderMultiMedia ID="id-289974777" referencedObject="ID_05837d80-7a54-4d3b-9cdf-1c56201bdfc6"/> </td> <td valign="middle"> <paragraph>After injection, maintain pressure on the plunger head and remove the needle from the skin. Release pressure on the plunger head to allow the needle guard to cover the needle. <content styleCode="bold">Do not re-cap the prefilled syringe.</content> </paragraph> </td> </tr> <tr styleCode="Botrule"> <td valign="top"> <paragraph>6</paragraph> </td> <td colspan="2" valign="top"> <paragraph>Discard the used syringe into a sharps container.</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20240917"/> <component> <observationMedia ID="ID_18259d26-043f-4e87-8e3c-3b0f29a353e7"> <text>figure1_10mg_and30mg_prefilled_syringe</text> <value mediaType="image/jpeg"> <reference value="figure_1_10mg_and 30mg_prefilled_syringe.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="C742B361-4234-44D7-8BBA-115C27F5E181"> <text>Figure 1 prefilled syringe components</text> <value mediaType="image/jpeg"> <reference value="image-01.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="C6E3C808-FE0A-4AE0-9C65-0B29427F16C2"> <text>Step 2 needle cover image</text> <value mediaType="image/jpeg"> <reference value="image-02.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="D7DDBF26-3C0F-4BFC-B678-C1BE0EBB9202"> <text>Step 3</text> <value mediaType="image/jpeg"> <reference value="image-03.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_7459ea9e-f5c4-4f96-8cf8-e4bd555b3b70"> <text>Step 4</text> <value mediaType="image/jpeg"> <reference value="image-04.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_05837d80-7a54-4d3b-9cdf-1c56201bdfc6"> <text>Step 5</text> <value mediaType="image/jpeg"> <reference value="image-05.jpg"/> </value> </observationMedia> </component> </section> </component> <component> <section ID="ID_79100255-b8ab-410a-9f71-f1ae3bbfb0b9"> <id root="23145453-ff78-49c2-8698-5ae1edac1c33"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.5 Instructions for Administration of FASENRA PEN </title> <text> <paragraph>Refer to the FASENRA PEN ‘Instructions for Use’ for more detailed instructions on the preparation and administration of FASENRA PEN <content styleCode="italics">[see Instructions for Use]</content>. A patient may self-inject or the patient’s caregiver may administer FASENRA PEN subcutaneously after the healthcare provider determines it is appropriate. In patients aged 6 to 11 years weighing 35 kg or more, FASENRA PEN should only be administered by a caregiver or healthcare provider.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_591a00d8-509b-472e-a6e1-0d858e64939b"> <id root="43b4c536-8ffa-4dd2-bfc0-0e7a02665a6c"/> <code code="43678-2" codeSystem="2.16.840.1.113883.6.1" displayName="DOSAGE FORMS & STRENGTHS SECTION"/> <title>3 DOSAGE FORMS AND STRENGTHS </title> <text> <paragraph>Injection: clear to opalescent, colorless to slightly yellow solution and may contain a few translucent or white to off‑white particles available as:</paragraph> <list listType="unordered"> <item> <caption>•</caption>10 mg/0.5 mL solution in a single-dose prefilled syringe.</item> <item> <caption>•</caption>30 mg/mL solution in a single-dose prefilled syringe.</item> <item> <caption>•</caption>30 mg/mL solution in a single-dose autoinjector FASENRA PEN.</item> </list> </text> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph>Injection:</paragraph> <list listType="unordered"> <item> <caption>•</caption>10 mg/0.5 mL solution in a single-dose prefilled syringe. (<linkHtml href="#ID_591a00d8-509b-472e-a6e1-0d858e64939b">3</linkHtml>)</item> <item> <caption>•</caption>30 mg/mL solution in a single-dose prefilled syringe. <linkHtml href="#ID_591a00d8-509b-472e-a6e1-0d858e64939b">(3)</linkHtml> </item> <item> <caption>•</caption>30 mg/mL solution in a single-dose autoinjector FASENRA PEN. <linkHtml href="#ID_591a00d8-509b-472e-a6e1-0d858e64939b">(3)</linkHtml> </item> </list> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_1d1c0d4c-48d8-428b-8e1f-8d0ad5efb978"> <id root="677e8c17-24c0-4bee-8782-ceddc0c9722c"/> <code code="34070-3" codeSystem="2.16.840.1.113883.6.1" displayName="CONTRAINDICATIONS SECTION"/> <title>4 CONTRAINDICATIONS </title> <text> <paragraph>FASENRA is contraindicated in patients who have known hypersensitivity to benralizumab or any of its excipients <content styleCode="italics">[see <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">Warnings and Precautions (5.1)</linkHtml>]</content>.</paragraph> </text> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph>Known hypersensitivity to benralizumab or excipients. <linkHtml href="#ID_1d1c0d4c-48d8-428b-8e1f-8d0ad5efb978">(4)</linkHtml> </paragraph> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_dfa97d43-c6d9-457b-9814-278f29a6ef61"> <id root="3b0f5d1f-5a85-41b5-9adb-8c60ee4ea50f"/> <code code="43685-7" codeSystem="2.16.840.1.113883.6.1" displayName="WARNINGS AND PRECAUTIONS SECTION"/> <title>5 WARNINGS AND PRECAUTIONS </title> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <list listType="unordered"> <item> <caption>•</caption>Hypersensitivity reactions: Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. Discontinue in the event of a hypersensitivity reaction. <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">(5.1)</linkHtml> </item> <item> <caption>•</caption>Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Decrease corticosteroids gradually, if appropriate. <linkHtml href="#ID_b59be893-de47-44f2-8163-b1e2370ad85a">(5.3)</linkHtml> </item> <item> <caption>•</caption>Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until the parasitic infection resolves. <linkHtml href="#ID_4200498f-6565-4774-8bad-9233be72848c">(5.4)</linkHtml> </item> </list> </text> </highlight> </excerpt> <component> <section ID="ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34"> <id root="c9af805f-55df-4506-922b-60861dfa5471"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.1 Hypersensitivity Reactions </title> <text> <paragraph>Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred following administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, FASENRA should be discontinued <content styleCode="italics">[see <linkHtml href="#ID_1d1c0d4c-48d8-428b-8e1f-8d0ad5efb978">Contraindications (4)</linkHtml>]</content>.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_0ff3a4b3-435b-4226-86e0-b630d1484327"> <id root="0ff3a4b3-435b-4226-86e0-b630d1484327"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.2 Acute Asthma Symptoms or Deteriorating Disease </title> <text> <paragraph>FASENRA should not be used to treat acute asthma symptoms or acute exacerbations. Do not use FASENRA to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA.</paragraph> </text> <effectiveTime value="20171114"/> </section> </component> <component> <section ID="ID_b59be893-de47-44f2-8163-b1e2370ad85a"> <id root="171f9428-193f-42ab-bae8-496058c78c2d"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.3 Reduction of Corticosteroid Dosage </title> <text> <paragraph>Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_4200498f-6565-4774-8bad-9233be72848c"> <id root="1f49c7a6-68fa-4734-8cf3-da841e44d4ab"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.4 Parasitic (Helminth) Infection </title> <text> <paragraph>Eosinophils may be involved in the immunological response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if FASENRA will influence a patient’s response against helminth infections.</paragraph> <paragraph>Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving treatment with FASENRA and do not respond to anti-helminth treatment, discontinue treatment with FASENRA until infection resolves.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_01a56f2a-9c56-48d1-aabe-3ec1407cae35"> <id root="69540d24-4d6a-456c-9502-41bdf7f835f7"/> <code code="34084-4" codeSystem="2.16.840.1.113883.6.1" displayName="ADVERSE REACTIONS SECTION"/> <title>6 ADVERSE REACTIONS </title> <text> <paragraph>The following adverse reactions are described in greater detail in other sections:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Hypersensitivity Reactions <content styleCode="italics">[see <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">Warnings and Precautions (5.1)</linkHtml>]</content> </item> </list> <paragraph>Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.</paragraph> </text> <effectiveTime value="20240917"/> <excerpt> <highlight> <text> <paragraph>Most common adverse reactions (incidence greater than or equal to 5%) include headache and pharyngitis. <linkHtml href="#_6.2_Clinical_Trials">(6.1, 6.2)</linkHtml> </paragraph> <paragraph> <content styleCode="underline"> </content> </paragraph> <paragraph> <content styleCode="bold">To report SUSPECTED ADVERSE REACTIONS, contact </content> <content styleCode="bold">AstraZeneca at 1-800-236-9933</content> <content styleCode="bold"> or FDA at 1-800-FDA-1088 or <linkHtml href="http://www.fda.gov/medwatch">www.fda.gov/medwatch.</linkHtml> </content> </paragraph> </text> </highlight> </excerpt> <component> <section ID="ID_3cc7ba70-1f14-439d-984c-3fbab3c1946d"> <id root="e2e98ca5-a607-4db6-abc8-8d01ccce983f"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>6.1 Clinical Trials Experience </title> <text> <paragraph> <content styleCode="underline">Adult and Adolescent Patients 12 Years of Age and Older with Asthma</content> </paragraph> <paragraph>Across three clinical trials (SIROCCO, CALIMA, and ZONDA) for asthma, 1,808 patients received at least 1 dose of FASENRA <content styleCode="italics">[see </content> <content styleCode="italics"> <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14.1)</linkHtml> </content> <content styleCode="italics">]</content>. The data described below reflect exposure to FASENRA in 1,663 patients, including 1,556 exposed for at least 24 weeks and 1,387 exposed for at least 48 weeks. The safety exposure for FASENRA is derived from two Phase 3 placebo-controlled trials (SIROCCO and CALIMA) from 48 weeks duration [FASENRA every 4 weeks (n=841), FASENRA every 4 weeks for 3 doses, then every 8 weeks (n=822), and placebo (n=847)]. While a dosing regimen of FASENRA every 4 weeks was included in clinical trials, FASENRA administered every 4 weeks for 3 doses, then every 8 weeks thereafter is the recommended dose <content styleCode="italics">[<linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">see Dosage and Administration (2.1)</linkHtml>]</content>. The population studied was 12 to 75 years of age, of which 64% were female and 79% were White.</paragraph> <paragraph>Adverse reactions that occurred at greater than or equal to 3% incidence are shown in <content styleCode="bold">Table 2</content>.</paragraph> <table width="100%"> <caption>Table 2. Adverse Reactions with FASENRA with Greater than or Equal to 3% Incidence in Patients with Asthma (SIROCCO and CALIMA)</caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Adverse Reactions</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> </paragraph> <paragraph> <content styleCode="bold">(N=822)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=847)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Headache</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Pyrexia</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Pharyngitis</content> <footnote ID="_Ref465201163">Pharyngitis was defined by the following terms: ‘Pharyngitis’, ‘Pharyngitis bacterial’, ‘Viral pharyngitis’, ‘Pharyngitis streptococcal’.</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Hypersensitivity reactions</content> <footnote ID="_Ref465201251">Hypersensitivity Reactions were defined by the following terms: ‘Urticaria’, ‘Urticaria papular’, and ‘Rash’<content styleCode="italics"> [see <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">Warnings and Precautions (5.1)</linkHtml>]</content>.</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>3</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="italics">28-Week Trial</content> </paragraph> <paragraph>Adverse reactions from ZONDA with 28 weeks of treatment with FASENRA (n=73) or placebo (n=75) in which the incidence was more common in FASENRA than placebo include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%, respectively) <content styleCode="italics">[see </content> <content styleCode="italics"> <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14.1)</linkHtml> </content> <content styleCode="italics">]</content>. The frequencies for the remaining adverse reactions with FASENRA were similar to placebo.</paragraph> <paragraph> <content styleCode="italics">Injection Site Reactions in Patients with Asthma</content> </paragraph> <paragraph>In SIROCCO and CALIMA, the FASENRA 30 mg prefilled syringe was administered at the recommended dosage and injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.</paragraph> <paragraph> <content styleCode="underline">Pediatric Patients 6 to 11 Years of Age with Asthma</content> </paragraph> <paragraph>The safety data for FASENRA is based on a 48-week, open-label, parallel group, pharmacokinetic and pharmacodynamic trial (TATE) of 28 pediatric patients aged 6 to 11 years with severe asthma, and with an eosinophilic phenotype <content styleCode="italics">[see <linkHtml href="#ID_9d42e499-4c01-461c-aa86-a61725586176">Use in Specific Populations (8.4)</linkHtml> and <linkHtml href="#ID_aca702ed-5cff-4e82-8f3d-d08b259d2fc2">Clinical Pharmacology (12.2</linkHtml>,<linkHtml href="#ID_2285f438-f42c-4dcc-b0af-614e6781a966">12.3)</linkHtml>]</content>. Patients received subcutaneous dose of 10 mg (for those weighing less than 35 kg) or 30 mg (for those weighing 35 kg or more) of FASENRA administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter <content styleCode="italics">[see <linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">Dosage and Administration (2.1)</linkHtml>]</content>. No new safety signals were observed in these patients.</paragraph> <paragraph> <content styleCode="underline">Adult Patients with EGPA </content> </paragraph> <paragraph>The safety of FASENRA is based on 70 adult patients who received at least 1 dose of FASENRA 30 mg administered subcutaneously every 4 weeks in an active-controlled study of 52 weeks duration (MANDARA) <content styleCode="italics">[see <linkHtml href="#ID_bae11046-0406-4577-8bbb-240ca73ae870">Clinical Studies (14.2)</linkHtml>]</content>. The incidence of adverse reactions were consistent to those reported in asthma, with the exception of headache, which occurred in 17% of FASENRA-treated patients with EGPA. No new adverse reactions were identified.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_a961a356-318e-4823-90a4-4f043c135422"> <id root="755de4af-d04e-4e60-a4f9-975c41348100"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>6.2 Postmarketing Experience </title> <text> <paragraph>In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post-approval use of FASENRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to FASENRA or a combination of these factors.</paragraph> <paragraph> <content styleCode="italics">Immune System Disorders: Hypersensitivity reactions, including anaphylaxis</content>.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_9d06e5ea-a2b2-44da-83e7-d9ebee9fa495"> <id root="9d06e5ea-a2b2-44da-83e7-d9ebee9fa495"/> <code code="34073-7" codeSystem="2.16.840.1.113883.6.1" displayName="DRUG INTERACTIONS SECTION"/> <title>7 DRUG INTERACTIONS </title> <text> <paragraph>No formal drug interaction studies have been conducted.</paragraph> </text> <effectiveTime value="20171114"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_cbf8b3b3-c806-4c5f-b73d-c7f15ac5a259"> <id root="d0932faa-c37c-4e41-abbf-2ef390970794"/> <code code="43684-0" codeSystem="2.16.840.1.113883.6.1" displayName="USE IN SPECIFIC POPULATIONS SECTION"/> <title>8 USE IN SPECIFIC POPULATIONS </title> <effectiveTime value="20240917"/> <component> <section ID="ID_6348cf7f-fe3b-4a8b-a979-4614b4c0d335"> <id root="bcb6cb95-7ffa-429d-b424-68732a74daaa"/> <code code="42228-7" codeSystem="2.16.840.1.113883.6.1" displayName="PREGNANCY SECTION"/> <title>8.1 Pregnancy </title> <text> <paragraph> <content styleCode="underline">Risk Summary</content> </paragraph> <paragraph>The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV administration of benralizumab throughout pregnancy at doses that produced exposures up to approximately 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg SC [see <content styleCode="italics">Data</content>].</paragraph> <paragraph>In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.</paragraph> <paragraph> <content styleCode="underline">Clinical Considerations</content> </paragraph> <paragraph> <content styleCode="italics">Disease-Associated Maternal and/or Embryo/Fetal Risk</content> </paragraph> <paragraph>In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.</paragraph> <paragraph> <content styleCode="underline">Data</content> </paragraph> <paragraph> <content styleCode="italics">Animal Data</content> </paragraph> <paragraph>In a prenatal and postnatal development study, pregnant cynomolgus monkeys received benralizumab from beginning on GD20 to GD22 (dependent on pregnancy determination), on GD35, once every 14 days thereafter throughout the gestation period and 1-month postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 6.5 months after birth. There was no evidence of treatment-related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. Benralizumab concentrations were approximately equal in mothers and infants on postpartum day 7, but were lower in infants at later time points. Eosinophil counts were suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, recovery of eosinophil counts was not observed for one infant monkey during this period.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_c6dabb95-245e-4537-9796-62f6b3b4c1b8"> <id root="1a58790a-b36a-43e8-9104-aa6e8e375128"/> <code code="77290-5" codeSystem="2.16.840.1.113883.6.1" displayName="LACTATION SECTION"/> <title>8.2 Lactation </title> <text> <paragraph> <content styleCode="underline">Risk Summary</content> </paragraph> <paragraph>There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast fed infant and on milk production are not known. However, benralizumab is a humanized monoclonal antibody (IgG1/κ-class), and immunoglobulin G (IgG) is present in human milk in small amounts. If benralizumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to benralizumab are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_9d42e499-4c01-461c-aa86-a61725586176"> <id root="87789191-d510-456b-81f7-c2b449bbba0f"/> <code code="34081-0" codeSystem="2.16.840.1.113883.6.1" displayName="PEDIATRIC USE SECTION"/> <title>8.4 Pediatric Use </title> <text> <paragraph> <content styleCode="underline">Asthma</content> </paragraph> <paragraph>The safety and effectiveness of FASENRA for add-on maintenance treatment of patients with severe asthma and with an eosinophilic phenotype have been established in pediatric patients 6 years and older. Use of FASENRA for this indication is supported by evidence from the following: </paragraph> <paragraph> <content styleCode="italics">Adolescent Patients 12 to 17 Years of Age</content> </paragraph> <paragraph>Use of FASENRA in adolescents with severe asthma and with an eosinophilic phenotype is supported by evidence from SIROCCO (n=53) and CALIMA (n=55) that enrolled 108 adolescents aged 12 to 17 years (mean age 14 years, 42% female, White 82%, Asian 2%, Black or African American 4%) with asthma. Of these patients, 46 received placebo, 40 received 30 mg of FASENRA every 4 weeks for 3 doses, followed by every 8 weeks thereafter, and 22 received 30 mg of FASENRA every 4 weeks. Patients were required to weigh 40 kg or more and to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at baseline (pre-bronchodilator FEV<sub>1</sub><90%) despite regular treatment with medium or high dose ICS and LABA with or without OCS or other controller therapy <content styleCode="italics">[see <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14)</linkHtml>]</content>. The pharmacokinetics of benralizumab in adolescents 12 to 17 years of age were consistent with adults based on population pharmacokinetic analysis and the reduction in blood eosinophil counts was similar to that observed in adults following the same FASENRA treatment. The adverse reaction profile in adolescents was generally similar to the overall population in the clinical trials <content styleCode="italics">[see <linkHtml href="#ID_3cc7ba70-1f14-439d-984c-3fbab3c1946d">Adverse Reactions (6.1)</linkHtml>]</content>.</paragraph> <paragraph> <content styleCode="underline">Pediatric Patients 6 to 11 Years of Age</content> </paragraph> <paragraph>Use of FASENRA in pediatric patients aged 6 to 11 years with severe asthma, and with an eosinophilic phenotype is supported by evidence from adequate and well-controlled trials in adults and adolescents with additional pharmacokinetic, pharmacodynamic, and safety data in pediatric patients aged 6 to 11 years. The effectiveness of FASENRA in pediatric patients 6 to 11 years of age is extrapolated from efficacy in three clinical trials (SIROCCO, CALIMA, and ZONDA) <content styleCode="italics">[see <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14)</linkHtml>]</content> with support from pharmacokinetic analysis and pharmacodynamic response in pediatric patients aged 6 to 11 years compared to adults and adolescents. TATE is a 48-week, open-label, pharmacokinetic and pharmacodynamic trial that was conducted in 28 patients aged 6 to 11 years (mean age 9 years; 6-8 years, n=11; 9-11 years n=17; 32% female, White 29%, Asian 32%, Black or African American 29%) with severe asthma, and with an eosinophilic phenotype.</paragraph> <paragraph>Based upon the pharmacokinetic data from TATE, a subcutaneous dose of 10 mg (patients <35 kg) and subcutaneous dose of 30 mg (patients ≥35 kg) of benralizumab administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter in patients aged 6 to 11 years was determined to have similar or higher exposure, respectively, to adults and adolescents administered a subcutaneous dose of 30 mg with the same dosing regimen <content styleCode="italics">[see <linkHtml href="#ID_2285f438-f42c-4dcc-b0af-614e6781a966">Clinical Pharmacology (12.3)</linkHtml>]</content>. The pharmacodynamic response observed in TATE for pediatric patients aged 6 to 11 years was similar to that observed in adults and adolescents <content styleCode="italics">[see <linkHtml href="#ID_aca702ed-5cff-4e82-8f3d-d08b259d2fc2">Clinical Pharmacology (12.2)</linkHtml>]</content>. No new safety signals were observed from TATE and safety for the higher drug exposure is supported by safety data from SIROCCO and CALIMA in adults and adolescents, and ZONDA in adults, who received 30 mg of FASENRA every 4 weeks for 1 year.</paragraph> <paragraph>The safety and effectiveness in patients younger than 6 years of age have not been established.</paragraph> <paragraph> <content styleCode="underline">EGPA</content> </paragraph> <paragraph>The safety and effectiveness of FASENRA in patients with EGPA younger than 18 years of age have not been established.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_1fa2a0c9-b44b-4a52-91a0-04591a9d11b1"> <id root="a9db693e-78b3-43e2-898d-e0b428f63a31"/> <code code="34082-8" codeSystem="2.16.840.1.113883.6.1" displayName="GERIATRIC USE SECTION"/> <title>8.5 Geriatric Use </title> <text> <paragraph> <content styleCode="underline">Asthma</content> </paragraph> <paragraph>Of the total number of patients in asthma clinical trials of benralizumab, 13% (n=320) were 65 and over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.</paragraph> <paragraph> <content styleCode="underline">EGPA</content> </paragraph> <paragraph>Of the 70 patients with EGPA exposed to FASENRA, a total of 13 (19%) were 65 years or older. Clinical studies of FASENRA for EGPA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_0f42d6cf-ae45-40b6-81a5-c0fc6c07d1b4"> <id root="fabca7cd-b547-460e-a6b5-376abc7eb7d9"/> <code code="34088-5" codeSystem="2.16.840.1.113883.6.1" displayName="OVERDOSAGE SECTION"/> <title>10 OVERDOSAGE </title> <text> <paragraph>There is no specific treatment for an overdosage with benralizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.</paragraph> </text> <effectiveTime value="20240917"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_24d2a8c2-e64b-463e-aed3-78a51897e008"> <id root="b2d302a6-e209-44c7-b145-c11af6b00db5"/> <code code="34089-3" codeSystem="2.16.840.1.113883.6.1" displayName="DESCRIPTION SECTION"/> <title>11 DESCRIPTION </title> <text> <paragraph>Benralizumab is a humanized monoclonal antibody (IgG1/κ-class) selective for interleukin-5 receptor alpha subunit (IL-5Rα). Benralizumab is produced in Chinese hamster ovary cells by recombinant DNA technology. Benralizumab has a molecular weight of approximately 150 kDa.</paragraph> <paragraph>FASENRA (benralizumab) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for subcutaneous injection. Since benralizumab is a protein, a few translucent or white to off-white particles may be present in the solution.</paragraph> <paragraph>Each 10 mg single-dose prefilled syringe delivers 0.5 mL containing 10 mg benralizumab, L-histidine (0.7 mg); L-histidine hydrochloride monohydrate (1.2 mg); polysorbate 20 (0.03 mg); α,α‑trehalose dihydrate (47 mg); and Water for Injection, USP, at pH of 5.5 – 6.5. The single-dose prefilled syringe contains a 1 mL glass syringe with a staked 29 gauge ½ inch stainless steel needle.</paragraph> <paragraph>Each 30 mg single-dose prefilled syringe or single-dose autoinjector delivers 1 mL containing 30 mg benralizumab, L-histidine (1.4 mg); L-histidine hydrochloride monohydrate (2.3 mg); polysorbate 20 (0.06 mg); α,α‑trehalose dihydrate (95 mg); and Water for Injection, USP, at pH of 5.5 – 6.5. The single-dose prefilled syringe or single-dose autoinjector contains a 1 mL glass syringe with a staked 29 gauge ½ inch stainless steel needle.</paragraph> </text> <effectiveTime value="20240917"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_80eecf04-dcd6-44bf-b024-b68ea33ec9b3"> <id root="710ad19e-6839-4ad8-ab7b-1513cfe29728"/> <code code="34090-1" codeSystem="2.16.840.1.113883.6.1" displayName="CLINICAL PHARMACOLOGY SECTION"/> <title>12 CLINICAL PHARMACOLOGY </title> <effectiveTime value="20240917"/> <component> <section ID="ID_9c84c3d1-b11b-48f1-a81f-ff07ec0ebcb1"> <id root="1b18f3c4-7a17-457e-98d1-2a95624696e0"/> <code code="43679-0" codeSystem="2.16.840.1.113883.6.1" displayName="MECHANISM OF ACTION SECTION"/> <title>12.1 Mechanism of Action </title> <text> <paragraph>Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an <content styleCode="italics">in vitro</content> setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcɣRIII receptors on immune effector cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC).</paragraph> <paragraph>Inflammation is an important component in the pathogenesis of asthma and EGPA. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Benralizumab, by binding to the IL-5Rα chain, reduces eosinophils through ADCC; however, the mechanism of benralizumab action in asthma and EGPA has not been definitively established.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_aca702ed-5cff-4e82-8f3d-d08b259d2fc2"> <id root="883a7b75-9cc5-4232-8147-b3a750817728"/> <code code="43681-6" codeSystem="2.16.840.1.113883.6.1" displayName="PHARMACODYNAMICS SECTION"/> <title>12.2 Pharmacodynamics </title> <text> <paragraph>In the 52-week Phase 2 dose-ranging trial, asthma patients received 1 of 3 doses of benralizumab [2 mg (n=81), 20 mg (n=81), or 100 mg (n=222)] or placebo (n=222). All doses were administered every 4 weeks for the first 3 doses, followed by every 8 weeks thereafter. Median blood eosinophil levels at baseline were 310, 280, 190 and 190 cells/μL in the 2, 20, and 100 mg benralizumab and placebo groups, respectively. Dose-dependent reductions in blood eosinophils were observed. At the time of the last dose (Week 40), median blood eosinophil counts were 100, 50, 40, 170 cells/μL in the 2, 20, and 100 mg benralizumab and placebo groups, respectively.</paragraph> <paragraph>A reduction in blood eosinophil counts was observed 24 hours post dosing in an asthma Phase 2 trial.</paragraph> <paragraph>In SIROCCO and CALIMA, following SC administration of benralizumab at the recommended dose blood eosinophils were reduced to a median absolute blood eosinophil count of 0 cells/μL <content styleCode="italics">[see <linkHtml href="#ID_14111a4b-ee97-4760-aac0-5d7849293693">Clinical Studies (14)</linkHtml>]</content>. This magnitude of reduction was observed at the first time point, 4 weeks of treatment, and was maintained throughout the treatment period.</paragraph> <paragraph>Treatment with benralizumab was also associated with reductions in blood basophils, which was consistently observed across all asthma clinical studies. In the Phase 2 dose-ranging asthma trial, blood basophil counts were measured by flow cytometry. Median blood basophil counts were 45, 52, 46, and 40 cells/µL in the 2 mg, 20 mg and 100 mg benralizumab and placebo groups, respectively. At 52 weeks (12 weeks after the last dose), median blood basophil counts were 42, 18, 17, and 46 cells/µL in the 2 mg, 20 mg and 100 mg benralizumab and placebo groups, respectively.</paragraph> <paragraph>In TATE, a 48-week trial with patients aged 6 to 11 years who had severe asthma, and with an eosinophilic phenotype <content styleCode="italics">[see <linkHtml href="#ID_9d42e499-4c01-461c-aa86-a61725586176">Use in Specific Populations (8.4)</linkHtml>]</content>, the magnitude of blood eosinophil reduction was similar to that observed in adults and adolescents. Median blood eosinophil levels at baseline were 400 and 340 cells/µL in patients weighing <35 kg and ≥35 kg, respectively. Across all post-dose time points, median eosinophil counts reduced to 10 to 20 cells/µL in patients weighing <35 kg, and to 20 to 30 cells/µL in patients weighing ≥35 kg. Blood eosinophil reduction was observed at the first time point, 4 weeks of treatment, and was maintained throughout the treatment period.</paragraph> <paragraph>In patients with EGPA, reduction of blood eosinophils was consistent with the effect observed in asthma trials. Median absolute blood eosinophil levels in the benralizumab group at baseline were 240 cells/μL. Following SC administration of benralizumab at the recommended dosage in patients with EGPA, blood eosinophils were reduced to a median absolute blood eosinophil count of 20 to 30 cells/μL. Blood eosinophil reduction was seen at the first observed time point, 1 week of treatment, and was maintained throughout the 52‑week treatment period.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_2285f438-f42c-4dcc-b0af-614e6781a966"> <id root="7767aa45-6cce-4f4f-b489-6783e7602481"/> <code code="43682-4" codeSystem="2.16.840.1.113883.6.1" displayName="PHARMACOKINETICS SECTION"/> <title>12.3 Pharmacokinetics </title> <text> <paragraph>The pharmacokinetic properties of benralizumab below are based on the population pharmacokinetic analyses from the asthma trials. Findings in EGPA were generally consistent with those in asthma although a lower clearance is predicted for patients with EGPA relative to patients with asthma <content styleCode="italics">[see Elimination]</content>. </paragraph> <paragraph>The pharmacokinetics of benralizumab was approximately dose-proportional in adult and adolescent patients with asthma following subcutaneous administration over a dose range of 20 to 200 mg.</paragraph> <paragraph> <content styleCode="underline">Absorption</content> </paragraph> <paragraph>Following subcutaneous administration to patients with asthma, the absorption half-life was approximately 3.5 days. Based on population pharmacokinetic analysis, the estimated absolute bioavailability was approximately 59% and there was no clinically relevant difference in relative bioavailability in the administration to the abdomen, thigh, or arm.</paragraph> <paragraph> <content styleCode="underline">Distribution</content> </paragraph> <paragraph>Based on population pharmacokinetic analysis, central and peripheral volume of distribution of benralizumab was 3.1 L and 2.5 L, respectively, for a 70 kg individual.</paragraph> <paragraph> <content styleCode="underline">Elimination</content> </paragraph> <paragraph>From population pharmacokinetic analysis, benralizumab exhibited linear pharmacokinetics and no evidence of target receptor-mediated clearance pathway. The estimated typical systemic clearance (CL) for benralizumab was 0.29 L/d for an asthma patient weighing 70 kg. The estimated typical CL was 0.22 L/d for patients with EGPA. Following subcutaneous administration in patients with asthma, the elimination half-life was approximately 15.5 days.</paragraph> <paragraph> <content styleCode="italics">Metabolism</content> </paragraph> <paragraph>Benralizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.</paragraph> <paragraph> <content styleCode="underline">Specific populations:</content> </paragraph> <paragraph> <content styleCode="italics">Age</content> </paragraph> <paragraph>Based on population pharmacokinetic analysis, age did not affect benralizumab clearance.</paragraph> <paragraph> <content styleCode="italics">Gender, Race</content> </paragraph> <paragraph>A population pharmacokinetics analysis indicated that there was no significant effect of gender and race on benralizumab clearance.</paragraph> <paragraph> <content styleCode="italics">Patients with Renal impairment</content> </paragraph> <paragraph>No formal clinical studies have been conducted to investigate the effect of renal impairment on benralizumab. Based on population pharmacokinetic analysis, benralizumab clearance was comparable in subjects with creatinine clearance values between 30 and 80 mL/min and patients with normal renal function. There are limited data available in subjects with creatinine clearance values less than 30 mL/min; however, benralizumab is not cleared renally.</paragraph> <paragraph> <content styleCode="italics">Patients with Hepatic impairment</content> </paragraph> <paragraph>No formal clinical studies have been conducted to investigate the effect of hepatic impairment on benralizumab. IgG monoclonal antibodies are not primarily cleared via hepatic pathway; change in hepatic function is not expected to influence benralizumab clearance. Based on population pharmacokinetic analysis, baseline hepatic function biomarkers (ALT, AST, and bilirubin) had no clinically relevant effect on benralizumab clearance.</paragraph> <paragraph> <content styleCode="italics">Pediatric Patients</content> </paragraph> <paragraph>Benralizumab pharmacokinetics following subcutaneous administration of 10 mg or 30 mg in patients aged 6 to 11 years with severe asthma and with an eosinophilic phenotype asthma was investigated in the initial 16-week treatment phase of TATE, a 48-week open-label trial. Among patients aged 6 to 11 years weighing <35 kg who received 10 mg, the median trough concentration at Week 16 was similar to that of adults and adolescents who received 30 mg. Among patients aged 6 to 11 years weighing ≥35 kg who received 30 mg, the median trough concentration at Week 16 was 62% higher relative to adults and adolescents receiving the same dose, due to lower body weight in pediatric patients.</paragraph> <paragraph> <content styleCode="underline">Drug Interaction Studies</content> </paragraph> <paragraph>No formal drug-drug interaction studies have been conducted.</paragraph> <paragraph>Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of benralizumab. There is no evidence of IL-5Rα expression on hepatocytes and eosinophil depletion does not produce chronic systemic alterations of proinflammatory cytokines.</paragraph> <paragraph>An effect of benralizumab on the pharmacokinetics of co-administered medications is not expected. Based on the population analysis, commonly co-administered medications had no effect on benralizumab clearance in patients with asthma.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> <component> <section ID="ID_7f5b6c04-752f-42a4-92a6-d688a8ff3662"> <id root="d9612390-ace3-490d-82ca-e06bcdbb905c"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>12.6 Immunogenicity </title> <text> <paragraph>The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of benralizumab or of other benralizumab products.</paragraph> <paragraph>In adult and adolescent patients with asthma, the incidence of ADA to benralizumab in patients treated with FASENRA at the recommended dosing regimen during the 48 to 56‑week treatment period was 13%. A total of 12% of patients treated with FASENRA developed neutralizing antibodies.</paragraph> <paragraph>In pediatric patients 6 to 11 years with severe asthma and with an eosinophilic phenotype, the incidence of ADA to benralizumab during an open-label 48-week treatment period was comparable to adult and adolescent patients. </paragraph> <paragraph>In patients with EGPA, the incidence of ADA to benralizumab during the active-controlled 52-week treatment period was 9% (6 out of 67 patients). Neutralizing antibody activity was detected in one of the ADA positive patients.</paragraph> <paragraph> <content styleCode="underline">Anti-Drug Antibody Effects on Pharmacokinetics and Pharmacodynamics</content> </paragraph> <paragraph>Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels in asthma patients with high ADA titers compared to antibody negative patients. Reduced benralizumab trough concentrations were observed in one EGPA patient with high ADA titers.</paragraph> <paragraph>In the asthma trials with adult and adolescent patients and in the EGPA trial, no evidence of an association of ADA with efficacy or safety was observed.</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_5a56631e-14a9-4f9a-820d-09bb04f86e12"> <id root="bda752fa-88ad-4a7b-91ed-d31318b0dda6"/> <code code="43680-8" codeSystem="2.16.840.1.113883.6.1" displayName="NONCLINICAL TOXICOLOGY SECTION"/> <title>13 NONCLINICAL TOXICOLOGY </title> <effectiveTime value="20240917"/> <component> <section ID="ID_302c93ac-b0d6-4b58-bac5-5bffb140f298"> <id root="40e709e2-5fe8-42c5-9310-e20f2f31f223"/> <code code="34083-6" codeSystem="2.16.840.1.113883.6.1" displayName="CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION"/> <title>13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility </title> <text> <paragraph>Long-term animal studies have not been performed to evaluate the carcinogenic potential of benralizumab. Published literature using animal models suggests that IL-5 and eosinophils are part of an early inflammatory reaction at the site of tumorigenesis and can promote tumor rejection. However, other reports indicate that eosinophil infiltration into tumors can promote tumor growth. Therefore, the malignancy risk in humans from an antibody that binds to IL-5Rα such as benralizumab is unknown.</paragraph> <paragraph>Male and female fertility were unaffected based upon no adverse histopathological findings in the reproductive organs from cynomolgus monkeys treated with benralizumab for 9 months at IV doses up to 25 mg/kg or at SC doses of up to 30 mg/kg once every 2 weeks (approximately 400 and 270 times the MRHD on an AUC basis).</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_14111a4b-ee97-4760-aac0-5d7849293693"> <id root="ff891bfb-0ad5-40ea-95d3-c6e960aca57a"/> <code code="34092-7" codeSystem="2.16.840.1.113883.6.1" displayName="CLINICAL STUDIES SECTION"/> <title>14 CLINICAL STUDIES </title> <effectiveTime value="20240917"/> <component> <section ID="ID_96fea628-a435-49b2-8dee-acfd071be3bc"> <id root="5f506dc6-1e83-4887-9d48-6dd94e60881c"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>14.1 Clinical Studies in Patients with Asthma </title> <text> <paragraph>The efficacy of FASENRA for the add-on maintenance treatment of severe asthma, and with an eosinophilic phenotype was evaluated in two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO (NCT01928771) and CALIMA (NCT01914757), for 48 and 56 weeks in duration, respectively. Furthermore, the effects of FASENRA in the reduction of oral corticosteroid use and effect on lung function were evaluated in clinical trials, ZONDA (NCT02075255) and a 12-week lung function trial (NCT02322775), respectively.</paragraph> <paragraph>SIROCCO and CALIMA were randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials in patients 12 years of age and older and 48 and 56 weeks in duration, respectively. The trials randomized a total of 2,510 patients. Patients were required to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months, ACQ‑6 score of 1.5 or more at screening, and reduced lung function at baseline [pre-bronchodilator FEV1 below 80% in adults, and below 90% in adolescents] despite regular treatment with high dose ICS (SIROCCO) or with medium or high dose ICS (CALIMA) plus a long-acting beta agonist (LABA) with or without oral corticosteroids (OCS) and additional asthma controller medications. Patients were stratified by geography, age, and blood eosinophils count (≥300 cells/μL or <300 cells/μL). FASENRA administered once every 4 weeks for the first 3 doses, and then every 4 or 8 weeks thereafter as add-on to background treatment was evaluated compared to placebo.</paragraph> <paragraph>All subjects continued their background asthma therapy throughout the duration of the trials.</paragraph> <paragraph>ZONDA was a randomized, double-blind, parallel-group, OCS reduction trial in 220 adult patients with asthma. Patients were required treatment with daily OCS (7.5 to 40 mg per day) in addition to regular use of high-dose ICS and LABA with or without additional controller(s). The trial included an 8‑week run-in period during which the OCS was titrated to the minimum effective dose without losing asthma control. For the purposes of the OCS dose titration, asthma control was assessed by the investigator based on a patient’s FEV1, peak expiratory flow, nighttime awakenings, short-acting bronchodilator rescue medication use or any other symptoms that would require an increase in OCS dose. Baseline median OCS dose was similar across all treatment groups. Patients were required to have blood eosinophil counts greater than or equal to 150 cells/μL and a history of at least one exacerbation in the past 12 months. The baseline median OCS dose was 10 mg (range: 8 to 40 mg) for all 3 treatment groups (placebo, FASENRA every 4 weeks, and FASENRA every 4 weeks for the first 3 doses, and then once every 8 weeks).</paragraph> <paragraph>While 2 dosing regimens were studied in SIROCCO, CALIMA, and ZONDA, the recommended dosing regimen is 30 mg FASENRA administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter <content styleCode="italics">[see <linkHtml href="#ID_07b5e868-a789-491f-bed0-3726140b03c4">Dosage and Administration (2.1)</linkHtml>]</content>.</paragraph> <table width="100%"> <caption>Table 3. Demographics and Baseline Characteristics of Asthma Trials</caption> <col width="44%"/> <col width="21%"/> <col width="20%"/> <col width="15%"/> <thead> <tr> <th align="left" styleCode="Rrule Lrule Toprule " valign="top"/> <th align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">Total Population</content> </th> </tr> </thead> <tbody> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">SIROCCO</content> </paragraph> <paragraph> <content styleCode="bold">(N=1204)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">CALIMA</content> </paragraph> <paragraph> <content styleCode="bold">(N=1306)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">ZONDA</content> </paragraph> <paragraph> <content styleCode="bold">(N=220)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean age (yr)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>49</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>49</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>51</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Female (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>66</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>62</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>61</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>White (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>73</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>84</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>93</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Duration of asthma, median (yr)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>15</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>16</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>12</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Never smoked (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>80</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>78</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>79</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean baseline FEV<sub>1</sub> pre-bronchodilator (L)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.67</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.76</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.85</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean baseline % predicted FEV<sub>1</sub> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>57</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>58</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>60</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean post-SABA FEV<sub>1</sub>/FVC (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>66</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>65</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>62</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean baseline eosinophil count (cells/μL)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>472</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>472</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>575</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>Mean number of exacerbations in previous year</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>3</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="underline">Exacerbations</content> </paragraph> <paragraph>The primary endpoint for SIROCCO and CALIMA was the rate of asthma exacerbations in patients with baseline blood eosinophil counts of greater than or equal to 300 cells/μL who were taking high‑dose ICS and LABA. Asthma exacerbation was defined as a worsening of asthma requiring use of oral/systemic corticosteroids for at least 3 days, and/or emergency department visits requiring use of oral/systemic corticosteroids and/or hospitalization. For patients on maintenance oral corticosteroids, an asthma exacerbation requiring oral corticosteroids was defined as a temporary increase in stable oral/systemic corticosteroids for at least 3 days or a single depo-injectable dose of corticosteroids. In SIROCCO, 35% of patients receiving FASENRA experienced an asthma exacerbation compared to 51% on placebo. In CALIMA, 40% of patients receiving FASENRA experienced an asthma exacerbation compared to 51% on placebo <content styleCode="bold">(Table 4)</content>.</paragraph> <table width="100%"> <caption>Table 4. Rate of Exacerbations, SIROCCO and CALIMA (ITT Population)<footnote ID="_Ref170476793">Baseline blood eosinophil counts of greater than or equal to 300 cells/μL and taking high-dose ICS</footnote> </caption> <col width="18%"/> <col width="29%"/> <col width="12%"/> <col width="15%"/> <col width="26%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Trial</content> </paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Treatment</content> </paragraph> </td> <td colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Exacerbations per year</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"/> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"/> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Rate</content> </paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Difference</content> </paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Rate Ratio (95% CI)</content> </paragraph> </td> </tr> <tr> <td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">All exacerbations</content> </paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>SIROCCO</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnote ID="_Ref170476809">FASENRA 30 mg administered every 4 weeks for the first 3 doses, and every 8 weeks thereafter</footnote> (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.74</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>-0.78</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.49 (0.37, 0.64)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>Placebo (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.52</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>CALIMA</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnoteRef IDREF="_Ref170476809"/> (n=239)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.73</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>-0.29</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.72 (0.54, 0.95)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>Placebo (n=248)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.01</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"> <list listType="ordered"> <item> <caption> </caption> <content styleCode="bold">Exacerbations requiring hospitalization/emergency room visit</content> </item> </list> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>SIROCCO</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnoteRef IDREF="_Ref170476809"/> (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.09</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>-0.16</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.37 (0.20, 0.67)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>Placebo (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.25</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>CALIMA</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnoteRef IDREF="_Ref170476809"/> (n=239)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.12</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.02</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.23 (0.64, 2.35)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>Placebo (n=248)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.10</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Exacerbations requiring hospitalization</content> </paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>SIROCCO</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnoteRef IDREF="_Ref170476809"/> (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.07</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>-0.07</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.48 (0.22, 1.03)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>Placebo (n=267)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.14</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>CALIMA</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>FASENRA<footnoteRef IDREF="_Ref170476809"/> (n=239)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.07</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.02</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.48 (0.65, 3.37)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>Placebo (n=248)</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>0.05</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>--</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>--</paragraph> </td> </tr> </tbody> </table> <paragraph>The time to first exacerbation was longer for the patients receiving FASENRA compared with placebo in SIROCCO (<content styleCode="bold">Figure 2</content>). Similar findings were seen in CALIMA.</paragraph> <paragraph> <content styleCode="bold">Figure 2.</content> <content styleCode="bold">Kaplan-Meier Cumulative Incidence Curves for Time to First Exacerbation, SIROCCO</content> </paragraph> <content styleCode="underline"> <renderMultiMedia ID="id-1016304396" referencedObject="ID_55c196b8-8063-4fa4-a740-574d8a3f8d4f"/> </content> <paragraph>Subgroup analyses from SIROCCO and CALIMA identified patients with a higher prior exacerbation history and baseline blood eosinophil count as potential predictors of improved treatment response. Reductions in exacerbation rates were observed irrespective of baseline peripheral eosinophil counts; however, patients with a baseline blood eosinophil count ≥300 cells/μL showed a numerically greater response than those with counts <300 cells/μL. In both trials patients with a history of 3 or more exacerbations within the 12 months prior to FASENRA randomization showed a numerically greater exacerbation response than those with fewer prior exacerbations.</paragraph> <paragraph> <content styleCode="underline">Oral Corticosteroid Reduction</content> </paragraph> <paragraph>ZONDA evaluated the effect of FASENRA on reducing the use of maintenance oral corticosteroids in adult patients with asthma. The primary endpoint was percent reduction from baseline of the final OCS dose during Weeks 24 to 28, while maintaining asthma control (see definition of asthma control in trial description). Compared to placebo, patients receiving FASENRA achieved greater reductions in daily maintenance oral corticosteroid dose, while maintaining asthma control. The median percent reduction in daily OCS dose from baseline was 75% in patients receiving FASENRA (95% CI: 60, 88) compared to 25% in patients receiving placebo (95% CI: 0, 33). Reductions of 50% or higher in the OCS dose were observed in 48 (66%) patients receiving FASENRA compared to those receiving placebo 28 (37%). The proportion of patients with a mean final dose less than or equal to 5 mg at Weeks 24 to 28 was 59% for FASENRA and 33% for placebo (odds ratio 2.74, 95% CI: 1.41, 5.31). Only patients with an optimized baseline OCS dose of 12.5 mg or less were eligible to achieve a 100% reduction in OCS dose during the study. Of those patients, 52% (22 of 42) receiving FASENRA and 19% (8 of 42) on placebo achieved a 100% reduction in OCS dose. Exacerbations resulting in hospitalization and/or ER visit were also assessed as a secondary endpoint. In this 28-week trial, patients receiving FASENRA had 1 event while those on placebo had 14 events (annualized rate 0.02 and 0.32, respectively; rate ratio of 0.07, 95% CI: 0.01, 0.63).</paragraph> <paragraph> <content styleCode="underline">Lung Function</content> </paragraph> <paragraph>Change from baseline in mean FEV<sub>1</sub> was assessed in SIROCCO, CALIMA, and ZONDA as a secondary endpoint. Compared with placebo, FASENRA provided consistent improvements over time in the mean change from baseline in FEV<sub>1</sub> (<content styleCode="bold">Figure 3</content> and <content styleCode="bold">Table 5</content>).</paragraph> <paragraph> <content styleCode="bold">Figure 3. Mean Change from Baseline in Pre-Bronchodilator FEV<sub>1</sub> (L), CALIMA</content> </paragraph> <renderMultiMedia ID="id402269681" referencedObject="ID_2fdf78b2-a0bb-4700-b145-cd4c3b03d282"/> <table width="100%"> <caption>Table 5. Change from Baseline in Mean Pre-Bronchodilator FEV1 (L) at End of Trial<footnote ID="_Ref170476910">Week 48 in SIROCCO, Week 56 in CALIMA, Week 28 in ZONDA.</footnote> </caption> <col width="16%"/> <col width="84%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Trial</content> </paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Difference from Placebo in Mean Change from Pre-Bronchodilator Baseline FEV1 (L) (95% CI)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>SIROCCO</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.159 (0.068, 0.249) </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>CALIMA</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0.116 (0.028, 0.204)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>ZONDA</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>0.112 (-0.033, 0.258)</paragraph> </td> </tr> </tbody> </table> <paragraph>Subgroup analyses also showed greater improvements in FEV<sub>1</sub> in patients with higher baseline blood eosinophil counts and more frequent prior exacerbation history.</paragraph> <paragraph>The clinical program for FASENRA also included a 12-week, randomized, double-blind, placebo-controlled lung function trial conducted in 211 adult patients with mild to moderate asthma. Patients were treated with placebo or benralizumab 30 mg SC every 4 weeks for 3 doses. Lung function, as measured by the change from baseline in FEV<sub>1</sub> at Week 12 was improved in the benralizumab treatment group compared to placebo.</paragraph> <paragraph> <content styleCode="underline">Patient Reported Outcomes</content> </paragraph> <paragraph>The Asthma Control Questionnaire-6 (ACQ-6) and Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) were assessed in SIROCCO, CALIMA, and ZONDA. The responder rate for both measures was defined as improvement in score of 0.5 or more as threshold at the end of SIROCCO, CALIMA, and ZONDA (48, 56, and 28 weeks, respectively). In SIROCCO, the ACQ-6 responder rate for FASENRA was 60% vs 50% placebo (odds ratio 1.55; 95% CI: 1.09, 2.19). In CALIMA, the ACQ-6 responder rate for FASENRA was 63% vs 59% placebo (odds ratio 1.16; 95% CI: 0.80, 1.68). In SIROCCO, the responder rate for AQLQ(S)+12 for FASENRA was 57% vs 49% placebo (odds ratio 1.42; 95% CI: 0.99, 2.02), and in CALIMA, 60% FASENRA vs 59% placebo (odds ratio of 1.03; 95% CI: 0.70,1.51). Similar results were seen in ZONDA.</paragraph> </text> <effectiveTime value="20240917"/> <component> <observationMedia ID="ID_55c196b8-8063-4fa4-a740-574d8a3f8d4f"> <text>Figure 2</text> <value mediaType="image/jpeg"> <reference value="image-06.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_2fdf78b2-a0bb-4700-b145-cd4c3b03d282"> <text>figure_3_change_from_baseline_fev1</text> <value mediaType="image/jpeg"> <reference value="image-07.jpg"/> </value> </observationMedia> </component> </section> </component> <component> <section ID="ID_bae11046-0406-4577-8bbb-240ca73ae870"> <id root="3d1a9a7d-d7b2-4730-ac0e-70b86738a1f4"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>14.2 Clinical Studies in Patients with Eosinophilic Granulomatosis with Polyangiitis </title> <text> <paragraph>The efficacy of FASENRA for eosinophilic granulomatosis with polyangiitis (EGPA) was evaluated in a randomized, double-blind, active-controlled, noninferiority clinical trial (MANDARA [NCT04157348]) of 52‑weeks duration. The trial enrolled a total of 140 adults aged 18 years and older with EGPA. Patients were required to have asthma, eosinophilia (1,000 cells/uL or >10% of leukocytes) and a history of relapsing or refractory disease treated with background prednisolone/prednisone with or without immunosuppressive therapy. Patients were randomized to receive FASENRA 30 mg administered subcutaneously every 4 weeks or mepolizumab 300 mg administered subcutaneously every 4 weeks in addition to continued background therapy. Starting at Week 4, the oral corticosteroid (OCS) dose was tapered at the discretion of the investigator. The MANDARA trial was a non-inferiority trial and was not designed to assess whether FASENRA was superior to mepolizumab. The pre-specified noninferiority (NI) margin was a treatment difference of ‑25%. The secondary endpoints (accrued duration of remission, relapse, OCS reduction and the asthma control questionnaire-6) were not included in the pre-specified multiple testing procedure for statistical significance.</paragraph> <paragraph>The demographics and baseline characteristics of patients in MANDARA are provided in <content styleCode="bold">Table 6</content>.</paragraph> <table width="100%"> <caption>Table 6. Demographics and Baseline Characteristics of Patients with EGPA in the MANDARA Trial</caption> <col width="68%"/> <col width="32%"/> <thead> <tr> <th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <content styleCode="bold">MANDARA (N=140)</content> </th> </tr> </thead> <tbody> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Mean age (years) </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>52</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Female (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>60</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>White (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>79</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Asian (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>12</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Other (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hispanic or Latino (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Time since diagnosis of EGPA, years, mean (SD)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>5.2 (5.6)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>History of ≥1 confirmed relapse in past 2 years (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>79</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Refractory disease (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>60</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Baseline oral corticosteroid<footnote ID="_Ref170481246">Prednisone or prednisolone equivalent.</footnote> daily dose, mg, median (range)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>10 (5 - 40)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Baseline BVAS, median (range)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0 (0 – 18)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>BVAS=0 (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>52</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Receiving immunosuppressive therapy<footnote ID="_Ref170481275">Azathioprine, methotrexate, mycophenolic acid.</footnote> (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>36</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>ANCA positive<footnote ID="_Ref170481291">Anti-neutrophil cytoplasmic antibody (ANCA) positive historically or at screening.</footnote> (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>29</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Biopsy Evidence of Eosinophilic Vasculitis/Inflammation (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>38</paragraph> </td> </tr> <tr> <td colspan="2" valign="top"> <paragraph>SD=standard deviation; BVAS=Birmingham vasculitis activity score.</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="underline">Remission</content> </paragraph> <paragraph>The primary endpoint in MANDARA was the proportion of patients in remission, defined as Birmingham Vasculitis Activity Score (BVAS)=0 (no active vasculitis) plus prednisolone/prednisone dose ≤4 mg/day, at both Week 36 and Week 48. The BVAS is a clinician-completed tool, that is divided into 9 organ-based systems, to assess clinically active vasculitis that would likely require treatment, after exclusion of other causes. As shown in <content styleCode="bold">Table 7</content>, FASENRA demonstrated noninferiority to mepolizumab for the primary endpoint of remission and the components of remission.</paragraph> <table width="467.5pt"> <caption>Table 7. Remission and Components of Remission in Patients with EGPA in MANDARA Trial</caption> <col width="21%"/> <col width="14%"/> <col width="12%"/> <col width="14%"/> <col width="12%"/> <col width="14%"/> <col width="12%"/> <tbody> <tr> <td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Remission</content> </paragraph> <paragraph> <content styleCode="bold">(OCS≤4 mg/day +<br/>BVAS=0)</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">OCS≤4 mg/day</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">BVAS=0</content> </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnote ID="_Ref178163156">FASENRA 30 mg administered subcutaneously every 4 weeks.</footnote> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnote ID="_Ref178163278">Mepolizumab (Mepo) 300 mg administered subcutaneously every 4 weeks.</footnote> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnoteRef IDREF="_Ref178163156"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnoteRef IDREF="_Ref178163278"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnoteRef IDREF="_Ref178163156"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnoteRef IDREF="_Ref178163278"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Patients in remission at both Weeks 36 and 48</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Patients, n (%)<footnote ID="_Ref178163343">Model adjusted percentages.</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>41 (59)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>40 (57)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>43 (62)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>41 (58)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>58 (83)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>59 (84)</paragraph> </td> </tr> <tr> <td rowspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Differences in remission rate (%)<footnoteRef IDREF="_Ref178163343"/> </paragraph> <paragraph>(95% CI)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>2.7</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>4.1</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>-1.2</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>(-13, 18)<footnote ID="_Ref178163361">NI margin -25% with 2.5% 1 sided significance level. Since the lower bound of the 95% CI for the treatment difference was >-25%, effectiveness of FASENRA was demonstrated to be noninferior to the effectiveness of mepolizumab.</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>(-11, 19)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>(-13, 11)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>--</paragraph> </td> </tr> <tr> <td colspan="7" valign="top"> <paragraph>N=number of patients in analysis.</paragraph> </td> </tr> </tbody> </table> <paragraph>Using an alternative remission definition of BVAS=0 plus prednisolone/ prednisone ≤7.5 mg/day, consistent efficacy between groups for these endpoints was observed.</paragraph> <paragraph> <content styleCode="underline">Accrued Duration of Remission</content> </paragraph> <paragraph>Total accrued duration of remission was similar in FASENRA compared to mepolizumab (odds ratio 1.4, 95% CI: 0.75, 2.5). Results for accrued duration of remission are shown in Table 8. The proportion of patients achieving remission within the first 24 weeks of treatment and remaining in remission through Week 52 was 42% for FASENRA and 37% for mepolizumab (difference in responder rate 5.5%, 95% CI: -9.3, 20). This result was not statistically significant as there was no pre-specified multiple testing procedure.</paragraph> <table width="100%"> <caption>Table 8. Accrued Duration of Remission in Patients with EGPA in the MANDARA Trial</caption> <col width="25%"/> <col width="12%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <col width="13%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Remission</content> </paragraph> <paragraph> <content styleCode="bold">(OCS≤4 mg/day +</content> </paragraph> <paragraph> <content styleCode="bold">BVAS=0)</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">OCS≤4 mg/day</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">BVAS=0</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnote ID="_Ref178164018">FASENRA 30 mg administered subcutaneously every 4 weeks.</footnote> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnote ID="_Ref178164071">Mepolizumab (Mepo) 300 mg administered subcutaneously every 4 weeks.</footnote> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnoteRef IDREF="_Ref178164018"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnoteRef IDREF="_Ref178164071"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">FASENRA</content> <footnoteRef IDREF="_Ref178164018"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mepo</content> <footnoteRef IDREF="_Ref178164071"/> </paragraph> <paragraph> <content styleCode="bold">N=70</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Accrued duration over 52</content> <content styleCode="bold">weeks</content> <footnote ID="_Ref178164190">Not included in the pre-specified multiple testing procedure for statistical significance.</footnote> <content styleCode="bold">, n (%)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>0 weeks<footnote ID="_Ref178164224">Did not achieve remission at any point.</footnote> </paragraph> <paragraph>>0 to <12 weeks</paragraph> <paragraph>12 to <24 weeks</paragraph> <paragraph>24 to <36 weeks</paragraph> <paragraph>≥36 weeks</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>9 (13)</paragraph> <paragraph>12 (17)</paragraph> <paragraph>8 (11)</paragraph> <paragraph>21 (30)</paragraph> <paragraph>20 (29)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>15 (21)</paragraph> <paragraph>10 (14)</paragraph> <paragraph>8 (11)</paragraph> <paragraph>19 (27)</paragraph> <paragraph>18 (26)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>9 (13)</paragraph> <paragraph>10 (14)</paragraph> <paragraph>9 (13)</paragraph> <paragraph>19 (27)</paragraph> <paragraph>23 (33)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>12 (17)</paragraph> <paragraph>12 (17)</paragraph> <paragraph>8 (11)</paragraph> <paragraph>18 (26)</paragraph> <paragraph>20 (29)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0</paragraph> <paragraph>0</paragraph> <paragraph>2 (3)</paragraph> <paragraph>6 (9)</paragraph> <paragraph>62 (89)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>0</paragraph> <paragraph>2 (3)</paragraph> <paragraph>2 (3)</paragraph> <paragraph>7 (10)</paragraph> <paragraph>59 (84)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>Odds ratio<footnote ID="_Ref178164268">An odds ratio >1 favors FASENRA. This result was not statistically significant as there was no pre-specified multiple testing procedure.</footnote> <br/>(95% CI)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>1.4</paragraph> <paragraph>(0.75, 2.5)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>--</paragraph> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>1.4</paragraph> <paragraph>(0.74, 2.5)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>--</paragraph> <paragraph>--</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>1.5</paragraph> <paragraph>(0.54, 4.2)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>--</paragraph> <paragraph>--</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="underline">Relapse</content> </paragraph> <paragraph>The hazard ratio for time to first relapse (defined as worsening related to vasculitis, asthma, or sino-nasal symptoms requiring an increase in dose of corticosteroids or immunosuppressive therapy or hospitalization) was 0.98 (95% CI: 0.53, 1.8). Relapse was observed in 30% of patients on FASENRA and 30% of patients on mepolizumab. The annualized relapse rate was 0.50 for patients receiving FASENRA versus 0.49 for patients receiving mepolizumab (rate ratio 1.0, 95% CI: 0.56, 1.9). The types of relapse were consistent for patients receiving FASENRA or mepolizumab.</paragraph> <paragraph> <content styleCode="underline">Oral Corticosteroid Reduction</content> </paragraph> <paragraph>During Weeks 48 to 52, a 100% reduction in the OCS dose was observed in 41% of patients receiving FASENRA compared to 26% of those receiving mepolizumab (difference 16%, 95% CI: 0.67, 31). During Weeks 48 to 52, reductions of 50% or higher were observed in 86% of patients receiving FASENRA compared to 74% of those receiving mepolizumab (difference 12%, 95% CI: -0.57, 25). These results were not statistically significant as there was no pre‑specified multiple testing procedure.</paragraph> <paragraph> <content styleCode="underline">Asthma Control Questionnaire-6 (ACQ-6)</content> </paragraph> <paragraph>ACQ-6 is a 6-item questionnaire that is completed by the patient to measure the adequacy of asthma control and change in asthma control. The ACQ-6 responder rate during Weeks 48 to 52 (defined as a decrease in score of 0.5 or more compared with baseline) was 42% for FASENRA and 48% for mepolizumab (difference -6.2%, 95% CI: -19, 6.2).</paragraph> </text> <effectiveTime value="20240917"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_083a678a-2e1f-44f2-9828-3d0fbd88de4d"> <id root="2497bf68-854b-4b43-9847-75bf4a353226"/> <code code="34069-5" codeSystem="2.16.840.1.113883.6.1" displayName="HOW SUPPLIED SECTION"/> <title>16 HOW SUPPLIED/STORAGE AND HANDLING </title> <text> <paragraph> <content styleCode="underline">How Supplied</content> </paragraph> <paragraph>FASENRA (benralizumab) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution and may contain a few translucent or white to off-white particles, for subcutaneous injection supplied as a single-dose prefilled syringe or single-dose autoinjector. The prefilled syringe (including stopper and cap) and autoinjector are not made with natural rubber latex.</paragraph> <paragraph>FASENRA is available as:</paragraph> <paragraph> <content styleCode="italics">Single-Dose Prefilled Syringe</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Carton contains one 10 mg/0.5 mL single-dose prefilled syringe with a gray plunger rod: NDC 0310-1745-01</item> <item> <caption>•</caption>Carton contains one 30 mg/mL single-dose prefilled syringe with a blue plunger rod: NDC 0310-1730-30</item> </list> <paragraph> <content styleCode="italics">Single-Dose Autoinjector FASENRA PEN</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Carton contains one 30 mg/mL single-dose autoinjector: NDC 0310-1830-30</item> </list> <paragraph> <content styleCode="underline">Storage and Handling</content> </paragraph> <paragraph>Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.</paragraph> <paragraph>If needed, the prefilled syringe and autoinjector may be stored at room temperature up to 77°F (25°C) for a maximum of 14 days in the original carton to protect from light. Once removed from the refrigerator and brought to room temperature (up to 77°F [25°C]), the prefilled syringe and autoinjector must be used within 14 days or discarded.</paragraph> <paragraph>Do not freeze. Do not shake. Do not expose to heat.</paragraph> </text> <effectiveTime value="20240917"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_b0459d81-9fbf-47d1-8838-383a18627db2"> <id root="a9c1c2c8-d444-4e1f-b3be-3628b5cea4d5"/> <code code="34076-0" codeSystem="2.16.840.1.113883.6.1" displayName="INFORMATION FOR PATIENTS SECTION"/> <title>17 PATIENT COUNSELING INFORMATION </title> <text> <paragraph>Advise the patients and/or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use for FASENRA PEN) before the patient starts using FASENRA and each time the prescription is renewed as there may be new information they need to know.</paragraph> <paragraph> <content styleCode="underline">Administration Instructions</content> </paragraph> <paragraph>Instruct patients and/or caregivers on proper subcutaneous injection technique using the FASENRA PEN, including aseptic technique, and the preparation and administration of FASENRA PEN prior to use. Advise patients to follow sharps disposal recommendations <content styleCode="italics">[see Instructions for Use].</content> </paragraph> <paragraph> <content styleCode="underline">Hypersensitivity Reactions</content> </paragraph> <paragraph>Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occurred within hours of FASENRA administration, but in some instances had a delayed onset (i.e., days). Instruct patients to contact their healthcare provider if they experience symptoms of an allergic reaction <content styleCode="italics">[see <linkHtml href="#ID_e6f2687b-7e19-4bc4-848f-e3b108d9ec34">Warnings and Precautions (5.1)</linkHtml>].</content> </paragraph> <paragraph> <content styleCode="underline">Not for Acute Symptoms or Deteriorating Disease</content> </paragraph> <paragraph>Inform patients that FASENRA does not treat acute asthma symptoms or acute exacerbations. Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA <content styleCode="italics">[see <linkHtml href="#ID_0ff3a4b3-435b-4226-86e0-b630d1484327">Warnings and Precautions (5.2)</linkHtml>]</content>.</paragraph> <paragraph> <content styleCode="underline">Reduction of Corticosteroid Dosage</content> </paragraph> <paragraph>Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a physician. Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy <content styleCode="italics">[see <linkHtml href="#ID_b59be893-de47-44f2-8163-b1e2370ad85a">Warnings and Precautions (5.3)</linkHtml>]</content>.</paragraph> <paragraph>Manufactured by</paragraph> <paragraph>AstraZeneca AB</paragraph> <paragraph>Södertälje, Sweden SE-15185</paragraph> <paragraph>US License No. 2059</paragraph> <paragraph>Distributed by</paragraph> <paragraph>AstraZeneca Pharmaceuticals LP,</paragraph> <paragraph>Wilmington, DE 19850</paragraph> <paragraph>FASENRA is a trademark of the AstraZeneca group of companies.</paragraph> <paragraph>©AstraZeneca 2024</paragraph> </text> <effectiveTime value="20240917"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_d2aaba75-0364-4796-a4d1-a715b63861fa"> <id root="26198614-a749-4dc0-9898-1321daf931ea"/> <code code="42230-3" codeSystem="2.16.840.1.113883.6.1" displayName="SPL PATIENT PACKAGE INSERT SECTION"/> <text> <table cellpadding="2.25pt" width="100.1%"> <col width="100%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Patient Information</content> </paragraph> <paragraph> <content styleCode="bold">FASENRA<sup>® </sup>(fas-en-rah)</content> </paragraph> <paragraph> <content styleCode="bold">(benralizumab)</content> </paragraph> <paragraph> <content styleCode="bold">injection, for subcutaneous use</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">What is FASENRA?</content> </paragraph> <paragraph>FASENRA is a prescription medicine used:</paragraph> <list listType="unordered"> <item> <caption> </caption> <list listType="unordered"> <item> <caption>o</caption>with other asthma medicines for the maintenance treatment of asthma in people 6 years and older whose asthma is not controlled with their current asthma medicines. FASENRA helps prevent severe asthma attacks (exacerbations) and may improve your breathing.</item> <item> <caption>o</caption>to treat people 18 years and older with eosinophilic granulomatosis with polyangiitis (EGPA).</item> </list> </item> <item> <caption>•</caption>FASENRA reduces blood eosinophils. Eosinophils are a type of white blood cell that may contribute to your condition.</item> <item> <caption>•</caption>FASENRA is not used to treat sudden breathing problems. </item> <item> <caption>•</caption>Tell your healthcare provider if your asthma does not get better or if it gets worse after you start treatment with FASENRA.</item> </list> <paragraph>It is not known if FASENRA is safe and effective in children with asthma under 6 years of age.</paragraph> <paragraph>It is not known if FASENRA is safe and effective in children with EGPA under 18 years of age.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Do not use FASENRA</content> if you are allergic to benralizumab or any of the ingredients in FASENRA. See the end of this leaflet for a complete list of ingredients in FASENRA.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Before using FASENRA, tell your healthcare provider about all of your medical conditions, including if you:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>are taking oral or inhaled corticosteroid medicines. <content styleCode="bold">Do not</content> stop taking your corticosteroid medicines unless instructed by your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine to come back.</item> <item> <caption>•</caption>have a parasitic (helminth) infection.</item> <item> <caption>•</caption>are pregnant or plan to become pregnant. It is not known if FASENRA will harm your unborn baby. Tell your healthcare provider if you become pregnant during your treatment with FASENRA.</item> <item> <caption>•</caption>are breastfeeding or plan to breastfeed. It is not known if FASENRA passes into your breast milk. You and your healthcare provider should decide if you will use FASENRA and breastfeed. Talk to your healthcare provider about the best way to feed your baby if you use FASENRA.</item> </list> <paragraph> <content styleCode="bold">Tell your healthcare provider about all the medicines you take</content>, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</paragraph> <paragraph> <content styleCode="bold">Do not</content> stop taking your other medicines for your condition unless your healthcare provider tells you to.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">How will I use FASENRA?</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>FASENRA is injected under your skin (subcutaneously):<list listType="unordered"> <item> <caption>o</caption>one time every 4 weeks for the first 3 doses and then every 8 weeks, for asthma.</item> <item> <caption>o</caption>one time every 4 weeks for EGPA.</item> </list> </item> <item> <caption>•</caption>FASENRA comes in a single dose prefilled syringe and in a single dose autoinjector.</item> <item> <caption>•</caption>A healthcare provider will inject FASENRA using the single-dose prefilled syringe.</item> <item> <caption>•</caption>If your healthcare provider decides that you or a caregiver can give the injection of FASENRA, you or your caregiver should receive training on the right way to prepare and give the injection using the FASENRA PEN.</item> <item> <caption>•</caption>In people aged 6 to 11 years, FASENRA should only be given by a caregiver or healthcare provider. </item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> try to inject FASENRA until you have been shown the right way by your healthcare provider. <content styleCode="bold">See the detailed “Instructions for Use” that comes with FASENRA PEN for information on how to prepare and inject FASENRA</content>.</item> <item> <caption>•</caption>If you miss a dose of FASENRA, call your healthcare provider.</item> </list> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">What are the possible side effects of FASENRA?</content> </paragraph> <paragraph> <content styleCode="bold">FASENRA may cause serious side effects, including:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">allergic (hypersensitivity) reactions, including anaphylaxis. </content>Serious allergic reactions can happen after you get your FASENRA injection. Allergic reactions can sometimes happen hours or days after you get your injection. Tell your healthcare provider or get emergency help right away if you have any of the following symptoms of an allergic reaction:<list listType="unordered"> <item> <caption>o</caption>swelling of your face, mouth and tongue</item> <item> <caption>o</caption>breathing problems</item> <item> <caption>o</caption>fainting, dizziness, feeling lightheaded (low blood pressure)</item> <item> <caption>o</caption>rash</item> <item> <caption>o</caption>hives</item> </list> </item> </list> <paragraph> <content styleCode="bold">The most common side effects of FASENRA include </content>headache and sore throat.</paragraph> <paragraph>These are not all the possible side effects of FASENRA.</paragraph> <paragraph>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">How should I store FASENRA?</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Store FASENRA in the refrigerator between 36°F to 46°F (2°C to 8°C).</item> <item> <caption>•</caption>FASENRA may be stored at room temperature between 68°F to 77°F (20°C to 25°C) <content styleCode="bold">for up to 14 days</content>.</item> <item> <caption>•</caption>Once removed from the refrigerator and brought to room temperature FASENRA must be used within 14 days or thrown away.</item> <item> <caption>•</caption>Store FASENRA in the original carton until you are ready to use it to protect it from light.</item> <item> <caption>•</caption>Do not freeze FASENRA. Do not use FASENRA that has been frozen.</item> <item> <caption>•</caption>Do not expose FASENRA to heat.</item> <item> <caption>•</caption>Do not use FASENRA past the expiration date.</item> <item> <caption>•</caption> <content styleCode="bold">Keep FASENRA and all medicines out of the reach of children</content>.</item> </list> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">General information about the safe and effective use of FASENRA.</content> </paragraph> <paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use FASENRA for a condition for which it was not prescribed. Do not give FASENRA to other people, even if they have the same symptoms you have. It may harm them.</paragraph> <paragraph>You can ask your doctor or pharmacist for information about FASENRA that is written for healthcare providers.</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">What are the ingredients in FASENRA?</content> </paragraph> <paragraph> <content styleCode="bold">Active ingredient: </content>benralizumab</paragraph> <paragraph> <content styleCode="bold">Inactive ingredients: </content>L-histidine, L-histidine hydrochloride monohydrate, polysorbate 20, α,α-trehalose dihydrate, and Water for Injection</paragraph> <paragraph>Manufactured by: AstraZeneca AB, Södertälje, Sweden SE-15185</paragraph> <paragraph>U.S. License Number 2059</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>FASENRA is a trademark of the AstraZeneca group of companies.</paragraph> <paragraph>©AstraZeneca 2024</paragraph> <paragraph>For more information, go to <content styleCode="underline"> <linkHtml href="https://www.fasenra.com/">https://www.FASENRA.com</linkHtml> </content> or call 1-800-236-9933.</paragraph> </td> </tr> </tbody> </table> <paragraph>This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: September 2024</paragraph> </text> <effectiveTime value="20240917"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_74715ca7-fa0b-41e8-873d-8bc081dc8334"> <id root="78226539-d2b3-4540-8691-1019fa6e41e3"/> <code code="59845-8" codeSystem="2.16.840.1.113883.6.1" displayName="INSTRUCTIONS FOR USE SECTION"/> <text> <table width="540pt"> <col width="25%"/> <col width="8%"/> <col width="16%"/> <col width="2%"/> <col width="2%"/> <col width="15%"/> <col width="8%"/> <col width="2%"/> <col width="9%"/> <col width="13%"/> <tbody> <tr> <td align="center" colspan="10" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Instructions for Use</content> </paragraph> <paragraph> <content styleCode="bold">FASENRA PEN™ (fas-en-rah)</content> </paragraph> <paragraph> <content styleCode="bold">(benralizumab)</content> </paragraph> <paragraph> <content styleCode="bold">for Subcutaneous Injection</content> </paragraph> <paragraph> <content styleCode="bold">Single-dose Autoinjector</content> </paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph>Before using your FASENRA PEN, your healthcare provider should show you or your caregiver how to use it the right way.</paragraph> <paragraph>In people aged 6 to 11 years, FASENRA should only be given by a caregiver or healthcare provider.</paragraph> <paragraph> <content styleCode="bold">Read this Instructions for Use before you start using your FASENRA PEN and each time you get a refill</content>. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.</paragraph> <paragraph>If you or your caregiver have any questions, talk to your healthcare provider.</paragraph> <paragraph> <content styleCode="bold">Important information:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Store FASENRA in a refrigerator between</content> 36°F to 46°F (2°C to 8°C) <content styleCode="bold">in its original carton until you are ready to use it.</content> </item> <item> <caption>•</caption>FASENRA may be kept at room temperature between 68°F to 77°F (20°C to 25°C) for a maximum of 14 days.</item> <item> <caption>•</caption>Once removed from the refrigerator and brought to room temperature, FASENRA must be used within 14 days or thrown away (disposed of).</item> </list> </td> </tr> <tr> <td colspan="5" styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> use your FASENRA PEN if:</paragraph> <list listType="unordered"> <item> <caption>•</caption>it has been frozen</item> <item> <caption>•</caption>it has been dropped or damaged</item> <item> <caption>•</caption>the security seal on the carton has been broken</item> <item> <caption>•</caption>the expiration date (EXP) has passed</item> </list> </td> <td colspan="5" styleCode="Rrule " valign="top"> <paragraph> <content styleCode="bold">Do not:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>shake your FASENRA PEN</item> <item> <caption>•</caption>share or reuse your FASENRA PEN</item> <item> <caption>•</caption>expose your FASENRA PEN to heat</item> </list> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph>If any of these happen, throw away the FASENRA PEN in a puncture-resistant sharps disposal container and use a new FASENRA PEN.</paragraph> <paragraph>Each FASENRA PEN contains 1 dose of FASENRA that is for one time use only.</paragraph> <paragraph> <content styleCode="bold">Keep FASENRA and all medicines out of the sight and reach of children.</content> </paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Your FASENRA PEN</content> </paragraph> <paragraph> <content styleCode="bold">Do not </content>remove the cap until you have reached Step 6 of these instructions and are ready to inject FASENRA.</paragraph> </td> </tr> <tr> <td colspan="5" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id10889746" referencedObject="ID_1ea52a7b-a483-42d1-adc6-e6307ab587d4"/> </td> <td colspan="5" styleCode="Rrule " valign="middle"> <renderMultiMedia ID="id1115332225" referencedObject="F8EAF6AB-4E4F-4BFC-9737-E2F63C2ACCE9"/> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 1 – Gather supplies</content> </paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>1 FASENRA PEN from the refrigerator</item> <item> <caption>•</caption>1 alcohol wipe</item> <item> <caption>•</caption>1 cotton ball or gauze</item> <item> <caption>•</caption>1 bandage</item> <item> <caption>•</caption>1 puncture-resistant sharps disposal container. See Step 10 for instructions on how to throw away (dispose of) the used FASENRA PEN safely.</item> </list> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"/> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <renderMultiMedia ID="id617337287" referencedObject="D7FFF194-EF75-493F-91DE-6E71991A324D"/> </td> </tr> <tr> <td colspan="8" styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 2 – Prepare to use your FASENRA PEN</content> </paragraph> <paragraph> <content styleCode="bold">Check the expiration date (EXP). </content>Do not use if the expiration date has passed.</paragraph> <paragraph> <content styleCode="bold">Let FASENRA warm up at room temperature</content> between 68°F to 77°F (20°C to 25°C) <content styleCode="bold">for about 30 minutes before giving the injection.</content> </paragraph> <paragraph> <content styleCode="bold">Do not</content> warm the FASENRA PEN in any other way. For example, do not warm it in a microwave or hot water, or put it near other heat sources.</paragraph> <paragraph>Use FASENRA within 14 days of removing from the refrigerator. After 14 days, throw away the FASENRA PEN.</paragraph> <paragraph> <content styleCode="bold">Do not</content> remove the cap until you have reached Step 6.</paragraph> </td> <td colspan="2" styleCode="Rrule " valign="middle"> <renderMultiMedia ID="id763733760" referencedObject="FE52657C-C758-4984-9D5B-4D39FB14EAE4"/> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 3 – Check the liquid</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id-33046421" referencedObject="ID_653c6fbe-5521-4575-9d1c-af2904a41e67"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph> <content styleCode="bold">Look at the liquid in the FASENRA PEN through the viewing window.</content> The liquid should be clear and colorless to slightly yellow. It may contain small white particles.</paragraph> <paragraph> <content styleCode="bold">Do not</content> inject FASENRA if the liquid is cloudy, discolored, or contains large particles.</paragraph> <paragraph>You may see small air bubbles in the liquid. This is normal. You do not need to do anything about it.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 4 – Choose the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id1090354333" referencedObject="EAF4E4F3-448B-4E6E-AFD8-DCD38397467E"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph>If you are giving yourself the injection, the <content styleCode="bold">recommended injection site</content> is the front of your thigh or the lower part of your stomach (abdomen).</paragraph> <paragraph>A caregiver may inject you in the upper-arm, thigh, or abdomen. <content styleCode="bold">Do not</content> try to inject yourself in the arm.</paragraph> <paragraph>For each injection, choose a different site that is at least 1‑inch (3-cm) away from where you last injected.</paragraph> <paragraph> <content styleCode="bold">Do not</content> inject:</paragraph> <list listType="unordered"> <item> <caption>•</caption>into the 2-inch (5-cm) area around your bellybutton</item> <item> <caption>•</caption>where the skin is tender, bruised, scaly or hard</item> <item> <caption>•</caption>into scars or damaged skin</item> <item> <caption>•</caption>through clothing</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"/> <td colspan="8" styleCode="Rrule " valign="top"/> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 5 – Clean the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id-522777005" referencedObject="B0D07803-3946-44A6-ACBA-1B611E5C2388"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph>Wash your hands well with soap and water.</paragraph> <paragraph>Clean the injection site with an alcohol wipe in a circular motion. Let it air dry.</paragraph> <paragraph> <content styleCode="bold">Do not</content> touch the cleaned area before injecting.</paragraph> <paragraph> <content styleCode="bold">Do not</content> fan or blow on the cleaned area.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 6 – Pull off the cap</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id-813941653" referencedObject="FB001A24-477D-4445-9707-2283F77F599E"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph>Hold the FASENRA PEN with 1 hand. Carefully pull the cap straight off with your other hand.</paragraph> <paragraph>Put the cap aside to throw away later.</paragraph> <paragraph>The green needle guard is now exposed. It is there to prevent you from touching the needle.</paragraph> <paragraph> <content styleCode="bold">Do not</content> try to touch the needle or push on the needle guard with your finger.</paragraph> <paragraph> <content styleCode="bold">Do not</content> try to put the cap back on the FASENRA PEN. You could cause the </paragraph> <paragraph>injection to happen too soon or damage the needle.</paragraph> <paragraph>Complete the following steps right away after removing the cap.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 7 – Inject FASENRA</content> </paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph>Follow your healthcare providers instructions on how to inject. You can either gently pinch at the injection site or give the injection without pinching the skin.</paragraph> <paragraph>Inject FASENRA by following the steps in figures <content styleCode="bold">a, b, c,</content> and <content styleCode="bold">d</content>.</paragraph> <paragraph>Hold the FASENRA PEN in place for the entire injection.</paragraph> <paragraph> <content styleCode="bold">Do not</content> change the position of the FASENRA PEN after the injection has started.</paragraph> </td> </tr> <tr> <td styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id408822332" referencedObject="ID_56dd2664-56f0-4eaf-aaf8-83841a64d3fe"/> </td> <td colspan="3" valign="middle"> <renderMultiMedia ID="id-1310236929" referencedObject="BC1EB825-A312-4ABD-9A93-64030B1230DC"/> </td> <td colspan="3" valign="middle"> <renderMultiMedia ID="id-1229148421" referencedObject="ID_73b0aa4f-20a5-4bf9-abf7-dbdf18e3bac4"/> </td> <td colspan="3" styleCode="Rrule " valign="middle"> <renderMultiMedia ID="id1174539669" referencedObject="C16EAC11-C7D4-4C5B-B607-C06D728A45FD"/> </td> </tr> <tr> <td styleCode="Lrule " valign="middle"/> <td colspan="3" valign="middle"/> <td colspan="3" valign="middle"/> <td colspan="3" styleCode="Rrule " valign="middle"/> </tr> <tr> <td styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Position the FASENRA PEN at the injection site.</content> </paragraph> <paragraph>Place the needle guard of the FASENRA PEN flat against your skin (90 degree angle).</paragraph> <paragraph>Make sure you can see the viewing window.</paragraph> </td> <td colspan="3" valign="top"> <paragraph> <content styleCode="bold">Press down firmly.</content> </paragraph> <paragraph>You will hear a click. A <content styleCode="bold">‘click’</content> tells you the injection has started. The green plunger will move down in the viewing window during the injection.</paragraph> </td> <td colspan="3" valign="top"> <paragraph> <content styleCode="bold">Hold down firmly for 15 seconds.</content> </paragraph> <paragraph>You will hear a second <content styleCode="bold">‘click’</content>. The second click tells you the injection has finished. The green plunger will fill the viewing window.</paragraph> </td> <td colspan="3" styleCode="Rrule " valign="top"> <paragraph> <content styleCode="bold">Lift the FASENRA PEN straight up.</content> </paragraph> <paragraph>The needle guard will slide down and lock into place over the needle.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 8 – Check the viewing window</content> </paragraph> </td> </tr> <tr> <td colspan="2" rowspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id1343438711" referencedObject="ID_73761fa6-a63e-491d-a338-f2eef19a3ee7"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph>Check the viewing window to make sure all the liquid has been injected.</paragraph> <paragraph>If the green plunger does not fill the viewing window, you may not have received the full dose. If this happens or if you have any other concerns, call your healthcare provider.</paragraph> </td> </tr> <tr> <td valign="middle"> <list listType="ordered"> <item> <caption> </caption>Before Injection</item> </list> </td> <td colspan="3" valign="middle"> <renderMultiMedia ID="id471106497" referencedObject="ID_7cda7799-011c-491a-8583-ef7f53bba9d7"/> </td> <td colspan="3" valign="middle"> <renderMultiMedia ID="id-835297057" referencedObject="ID_9cf3ffe7-2a83-4085-bcdd-1d6c32b7d74c"/> </td> <td styleCode="Rrule " valign="middle"> <paragraph>After Injection</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 9 – Check the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id-1646424987" referencedObject="ID_7fd24111-a56d-45e3-8b48-f0afbb3d187b"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <paragraph>There may be a small amount of blood or liquid where you injected. This is normal.</paragraph> <paragraph>Gently hold pressure over your skin with a cotton ball or gauze until the bleeding stops.</paragraph> <paragraph> <content styleCode="bold">Do not</content> rub the injection site.</paragraph> <paragraph>If needed, cover the injection site with a small bandage.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 10 – Dispose of the used FASENRA PEN safely</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="middle"> <renderMultiMedia ID="id1391076356" referencedObject="FB02DC82-35EB-48D9-BF04-27B52E65451E"/> </td> <td colspan="8" styleCode="Rrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>Each FASENRA PEN contains a single dose of FASENRA and <content styleCode="bold">cannot be reused</content>.</item> <item> <caption>•</caption>Put your used FASENRA PEN in a FDA-cleared <content styleCode="bold">sharps disposal container</content> right away after use.</item> </list> <paragraph> <content styleCode="bold">Do not</content> throw away the FASENRA PEN in your household trash.</paragraph> <paragraph>Throw away the cap and other used supplies in your household trash.</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Disposal guidelines</content> </paragraph> <paragraph>If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:</paragraph> <list listType="unordered"> <item> <caption>•</caption>made of a heavy-duty plastic,</item> <item> <caption>•</caption>can be closed with a tight-fitting puncture-resistant lid, without sharps being able to come out,</item> <item> <caption>•</caption>upright and stable during use,</item> <item> <caption>•</caption>leak-resistant, and</item> <item> <caption>•</caption>properly labeled to warn of hazardous waste inside the container.</item> </list> <paragraph>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the area that you live in, go to the FDA’s website at: <content styleCode="underline"> <linkHtml href="https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/HomeHealthandConsumer/ConsumerProducts/Sharps/default.htm">http://www.fda.gov/safesharpsdisposal</linkHtml> </content>.</paragraph> <paragraph> <content styleCode="bold">Do not</content> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.</paragraph> <paragraph> <content styleCode="bold">Do not</content> recycle your used sharps disposal container.</paragraph> <paragraph>For more information go to <content styleCode="underline"> <linkHtml href="http://www.FasenraPen.com">www.FasenraPen.com</linkHtml> </content> or call 1-800-236-9933. If you still have questions, call your healthcare provider.</paragraph> <paragraph>Manufactured by: AstraZeneca AB, Södertälje, Sweden SE-15185</paragraph> <paragraph>U.S. License Number 2059</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>FASENRA is a trademark of the AstraZeneca group of companies.</paragraph> <paragraph>©AstraZeneca 2024</paragraph> <paragraph>This Instructions for Use has been approved by the U.S. Food and Drug Administration</paragraph> </td> </tr> <tr> <td colspan="10" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>Issued: April 2024</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20240917"/> <component> <observationMedia ID="ID_1ea52a7b-a483-42d1-adc6-e6307ab587d4"> <text>Your_Fasenra_Pen_Before_Use</text> <value mediaType="image/jpeg"> <reference value="your_fasenra_pen_before_use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="F8EAF6AB-4E4F-4BFC-9737-E2F63C2ACCE9"> <text>your_fasenra_pen_after_use</text> <value mediaType="image/jpeg"> <reference value="your_fasenra_pen_after_use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="D7FFF194-EF75-493F-91DE-6E71991A324D"> <text>step_1_gather_supplies</text> <value mediaType="image/jpeg"> <reference value="step_1_gather_supplies.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="FE52657C-C758-4984-9D5B-4D39FB14EAE4"> <text>Step_2_30_minute_clock</text> <value mediaType="image/jpeg"> <reference value="step_2_30_minute_clock.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_653c6fbe-5521-4575-9d1c-af2904a41e67"> <text>Step_3_Fasenra_Pen_viewing_window</text> <value mediaType="image/jpeg"> <reference value="step_3_fasenra_pen_viewing_window.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="EAF4E4F3-448B-4E6E-AFD8-DCD38397467E"> <text>step_4_choose_the_injection_site</text> <value mediaType="image/jpeg"> <reference value="step_4_choose_the_injection_site.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="B0D07803-3946-44A6-ACBA-1B611E5C2388"> <text>Step_5_Clean_the_injection_site</text> <value mediaType="image/jpeg"> <reference value="step_5_clean_the_injection_site.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="FB001A24-477D-4445-9707-2283F77F599E"> <text>Step_6_Pull_off_the_cap</text> <value mediaType="image/jpeg"> <reference value="step_6_pull_off_the_cap.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_56dd2664-56f0-4eaf-aaf8-83841a64d3fe"> <text>step_7_a_position_the_pen_at_the_injection_site</text> <value mediaType="image/jpeg"> <reference value="step_7_a_position_the_pen_at_the_injection_site.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="BC1EB825-A312-4ABD-9A93-64030B1230DC"> <text>step_7_b_position_press_down_firmly</text> <value mediaType="image/jpeg"> <reference value="step_7_b_position_press_down_firmly.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_73b0aa4f-20a5-4bf9-abf7-dbdf18e3bac4"> <text>step_7_c_hold_down_firmly_for_15_seconds</text> <value mediaType="image/jpeg"> <reference value="step_7_c_hold_down_firmly_for_15_seconds.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="C16EAC11-C7D4-4C5B-B607-C06D728A45FD"> <text>step_7_d_lift_the_fasenra_pen_straight_up</text> <value mediaType="image/jpeg"> <reference value="step_7_d_lift_the_fasenra_pen_straight_up.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_73761fa6-a63e-491d-a338-f2eef19a3ee7"> <text>step_8_check_the_viewing_window</text> <value mediaType="image/jpeg"> <reference value="step_8_check_the_viewing_window.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_7cda7799-011c-491a-8583-ef7f53bba9d7"> <text>step_8_viewing_window_before_injection</text> <value mediaType="image/jpeg"> <reference value="step_8_viewing_window_before_injection.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_9cf3ffe7-2a83-4085-bcdd-1d6c32b7d74c"> <text>step_8_viewing_window_after_injection</text> <value mediaType="image/jpeg"> <reference value="step_8_viewing_window_after_injection.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_7fd24111-a56d-45e3-8b48-f0afbb3d187b"> <text>step_9_check_the_injection_site</text> <value mediaType="image/jpeg"> <reference value="step_9_check_the_injection_site.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="FB02DC82-35EB-48D9-BF04-27B52E65451E"> <text>step_10_sharps_container</text> <value mediaType="image/jpeg"> <reference value="step_10_sharps_container.jpg"/> </value> </observationMedia> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_7280d2e2-a31d-4f20-aa9b-d2913eda674a"> <id root="39f5735f-0d1e-4611-b0ff-63b158e56424"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>PACKAGE/LABEL PRINCIPAL DISPLAY PANEL </title> <text> <paragraph> <content styleCode="bold">NDC 0310-1730-30 Rx only </content> </paragraph> <table width="100%"> <col width="56%"/> <col width="44%"/> <tbody> <tr styleCode="Toprule"> <td valign="top"> <paragraph> <content styleCode="bold">FASENRA<sup>®</sup> </content> </paragraph> <paragraph>(benralizumab) Injection</paragraph> <paragraph> <content styleCode="bold">For Subcutaneous Injection Only</content> </paragraph> <paragraph>Store the prefilled syringe refrigerated at 36°F - 46°F</paragraph> <paragraph>(2°C - 8°C) in original carton to protect from light.</paragraph> <paragraph>Do not shake, freeze, or expose to heat.</paragraph> </td> <td valign="top"> <paragraph> <content styleCode="bold">30 mg/mL</content> </paragraph> <paragraph> <content styleCode="bold">1 single-dose prefilled syringe</content> </paragraph> <paragraph>Discard unused portion.</paragraph> <paragraph>AstraZeneca</paragraph> </td> </tr> </tbody> </table> <renderMultiMedia ID="id-1648124494" referencedObject="ID_22d28331-9280-479f-b155-99ad577a811e"/> </text> <effectiveTime value="20240917"/> <component> <observationMedia ID="ID_22d28331-9280-479f-b155-99ad577a811e"> <text>fasenra-30mg-carton-sales</text> <value mediaType="image/jpeg"> <reference value="fasenra-30mg-carton-sales.jpg"/> </value> </observationMedia> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_85afb1ab-6346-4eba-a786-c95da50462af"> <id root="b954096f-793f-4c13-b05a-56e32487cb65"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>PACKAGE/LABEL PRINCIPAL DISPLAY PANEL </title> <text> <paragraph> <content styleCode="bold">NDC 0310-1745-01 Rx only </content> </paragraph> <table width="100%"> <col width="56%"/> <col width="44%"/> <tbody> <tr styleCode="Toprule"> <td valign="top"> <paragraph> <content styleCode="bold">FASENRA<sup>®</sup> </content> </paragraph> <paragraph>(benralizumab) Injection</paragraph> <paragraph> <content styleCode="bold">For Subcutaneous Injection Only</content> </paragraph> <paragraph>Store the prefilled syringe refrigerated at 36°F - 46°F</paragraph> <paragraph>(2°C - 8°C) in original carton to protect from light.</paragraph> <paragraph>Do not shake, freeze, or expose to heat.</paragraph> </td> <td valign="top"> <paragraph> <content styleCode="bold">10 mg/0.5 mL</content> </paragraph> <paragraph> <content styleCode="bold">1 single-dose prefilled syringe</content> </paragraph> <paragraph>Discard unused portion.</paragraph> <paragraph>AstraZeneca</paragraph> </td> </tr> </tbody> </table> <renderMultiMedia ID="id-939608854" referencedObject="FD4297AE-D6F3-4C8F-9AC6-B55FA8164C2A"/> </text> <effectiveTime value="20240917"/> <component> <observationMedia ID="FD4297AE-D6F3-4C8F-9AC6-B55FA8164C2A"> <text>fasenra-10mg-carton-sales</text> <value mediaType="image/jpeg"> <reference value="fasenra-10mg-carton-sales.jpg"/> </value> </observationMedia> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_1fb07fd0-60f5-4011-8f93-c71ddddba9d3"> <id root="2102e14c-3ced-4aec-aa5f-d2af53d9c6a5"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>Package/Label Display Panel </title> <text> <paragraph> <content styleCode="bold">NDC 0310-1830-30 Rx only </content> </paragraph> <table width="100%"> <col width="56%"/> <col width="44%"/> <tbody> <tr styleCode="Toprule"> <td valign="top"> <paragraph> <content styleCode="bold">FASENRA PEN™</content> </paragraph> <paragraph>(benralizumab) Injection</paragraph> <paragraph> <content styleCode="bold">For Subcutaneous Injection Only</content> </paragraph> <paragraph>Store the FASENRA PEN refrigerated at 36°F - 46°F (2°C - 8°C) in original carton to protect from light.</paragraph> <paragraph>Do not shake, freeze, or expose to heat.</paragraph> </td> <td valign="top"> <paragraph> <content styleCode="bold">30 mg/mL</content> </paragraph> <paragraph> <content styleCode="bold">1 single-dose prefilled autoinjector</content> </paragraph> <paragraph>Discard unused portion.</paragraph> <paragraph>AstraZeneca</paragraph> </td> </tr> </tbody> </table> <renderMultiMedia ID="id1004561800" referencedObject="ID_0d5d8603-2de1-4d6b-837d-6f9d05d1dca0"/> </text> <effectiveTime value="20191003"/> <component> <observationMedia ID="ID_0d5d8603-2de1-4d6b-837d-6f9d05d1dca0"> <text>FasenraPen-30mg_ml_single_dose_autoinjector_carton</text> <value mediaType="image/jpeg"> <reference value="fasenrapen-30mg_ml_single_dose_autoinjector_carton.jpg"/> </value> </observationMedia> </component> </section>

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