PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrNUCALA Mepolizumab for Injection 100 mg/mL lyophilized powder for subcutaneous injection Mepolizumab Injection 100 mg/mL solution for subcutaneous injection Interleukin-5 (IL-5) inhibitor GlaxoSmithKline Inc. 7333 Mississauga Road Mississauga, Ontario L5N 6L4 Date of Initial Approval: April 6, 2016 Date of Revision: September 14, 2021 Submission Control No: 244472 ©2021 GSK group of companies or its licensor Trademarks are owned by or licensed to the GSK group of companies Nucala September 14, 2021 Page 1 of 71 RECENT MAJOR LABEL CHANGES INDICATIONS (1) SEP, 2021 WARNINGS AND PRECAUTIONS, Special Populations (7.1.3) SEP, 2021 DOSAGE AND ADMINISTRATION, Hypereosinophilic Syndrome (3.3.3) SEP, 2021 DOSAGE AND ADMINISTRATION, Pediatrics (3.3.5) SEP, 2021 DOSAGE AND ADMINISTRATION, Dosing Considerations (3.1) MAR, 2020 DOSAGE AND ADMINISTRATION, Recommended Dose & Dosage Adjustment MAR, 2020 DOSAGE AND ADMINISTRATION, Administration (3.3) MAR, 2020 DOSAGE AND ADMINISTRATION, Missed Dose (3.5) MAR, 2020 WARNINGS AND PRECAUTIONS, Special Populations (7.1.1) NOV, 2019 PART I: HEALTH PROFESSIONAL INFORMATION.................................................................4 1 INDICATIONS .................................................................................................................4 1.1 Pediatrics (< 18 years of age)..................................................................................4 1.2 Geriatrics (≥ 65 years of age) ..................................................................................4 2 CONTRAINDICATIONS..................................................................................................5 3 DOSAGE AND ADMINISTRATION ................................................................................5 3.1 Dosing Considerations.............................................................................................5 3.2 Recommended Dose and Dosage Adjustment.......................................................5 3.3 Administration..........................................................................................................7 3.4 Reconstitution..........................................................................................................8 3.5 Missed Dose............................................................................................................9 4 OVERDOSAGE...............................................................................................................9 5 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .........................9 6 DESCRIPTION..............................................................................................................11 7 WARNINGS AND PRECAUTIONS ...............................................................................11 7.1 Special Populations ...............................................................................................12 7.1.1 Pregnant Women .............................................................................................12 7.1.2 Breast-feeding..................................................................................................12 7.1.3 Pediatrics (< 18 years of age)...........................................................................12 7.1.4 Geriatrics (≥ 65 years of age) ...........................................................................12 8 ADVERSE REACTIONS ...............................................................................................13 8.1 Adverse Reaction Overview.................................................................................13 8.2 Clinical Trial Adverse Reactions in subjects with Severe Eosinophilic Asthma.....13 8.3 Less Common Clinical Trial Adverse Reactions in Subjects with Severe Eosinophilic Asthma ......................................................................................................19 8.4 Clinical Trial Adverse Reactions in Subjects with Eosinophilic Granulomatosis with Polyangiitis (EGPA).......................................................................................................20 8.5 Less Common Clinical Trial Adverse Reactions in Subjects with EGPA...............23 8.6 Clinical Trial Adverse Reactions in Subjects with Hypereosinophilic Syndrome (HES)23 8.7 Less Common Clinical Trial Adverse Reactions in Subjects with HES .................25 8.8 Post-Market Adverse Reactions............................................................................26 9 DRUG INTERACTIONS ................................................................................................26 9.1 Overview ...............................................................................................................26 Nucala September 14, 2021 Page 2 of 71 9.2 Drug-Drug Interactions ..........................................................................................26 9.3 Drug-Food Interactions ..........................................................................................26 9.4 Drug-Herb Interactions ..........................................................................................26 9.5 Drug-Laboratory Test Interactions .........................................................................26 10 ACTION AND CLINICAL PHARMACOLOGY...............................................................26 10.1 Mechanism of Action ...........................................................................................26 10.2 Pharmacodynamics .............................................................................................27 10.3 Pharmacokinetics ................................................................................................28 11 STORAGE, STABILITY AND DISPOSAL.....................................................................30 12 SPECIAL HANDLING INSTRUCTIONS........................................................................31 PART II: SCIENTIFIC INFORMATION .....................................................................................32 13 PHARMACEUTICAL INFORMATION...........................................................................32 14 CLINICAL TRIALS........................................................................................................32 14.1 Trial Design and Study Demographics in Severe Eosinophilic Asthma ................32 14.2 Study Results for Clinical Trials in Severe Eosinophilic Asthma...........................36 14.3 Trial Design and Study Demographics for Clinical Trials in Eosinophilic Granulomatosis with Polyangiitis (EGPA) ......................................................................38 14.4 Study Results for Clinical Trials in EGPA.............................................................41 14.5 Trial Design and Study Demographics for Clinical Trials in Hypereosinophilic Syndrome (HES) ...........................................................................................................43 14.6 Study Results for Clinical Trials in HES ...............................................................44 15 NON-CLINICAL TOXICOLOGY....................................................................................46 PATIENT MEDICATION INFORMATION .................................................................................47 PATIENT MEDICATION INFORMATION .................................................................................53 INSTRUCTIONS FOR USE - Pre-Filled Autoinjector .............................................................59 INSTRUCTIONS FOR USE - Pre-Filled Safety Syringe..........................................................66 Nucala September 14, 2021 Page 3 of 71 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS Severe Eosinophilic Asthma NUCALA (mepolizumab for injection, mepolizumab injection) is indicated as add-on maintenance treatment for adults, adolescents, and children (aged 6 years and older) with severe eosinophilic asthma who: are inadequately controlled with high-dose inhaled corticosteroids (patients ≥ 18 years of age) or medium-to-high-dose inhaled corticosteroids (patients 6-17 years of age) and an additional asthma controller(s) (e.g., LABA); and have a blood eosinophil count of ≥ 150 cells/μL (0.15 GI/L) at initiation of treatment with NUCALA OR ≥ 300 cells/μL (0.3 GI/L) in the past 12 months. NUCALA is not indicated for the relief of acute bronchospasm or status asthmaticus (See WARNINGS AND PRECAUTIONS). Eosinophilic Granulomatosis with Polyangiitis NUCALA is indicated as an add-on to corticosteroids for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Hypereosinophilic Syndrome NUCALA is indicated as an add-on to standard therapy for the treatment of adult patients with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause. 1.1 Pediatrics (< 18 years of age) Severe Eosinophilic Asthma: NUCALA is not indicated in patients under 6 years of age. There is limited efficacy and safety experience with NUCALA in patients less than 18 years of age (see CLINICAL TRIALS Study Results for Clinical Trials in Severe Eosinophilic Asthma). Dosing in children was derived using modelling and simulation of adult and pediatric PK data (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Patient Populations). Eosinophilic Granulomatosis with Polyangiitis: NUCALA is not indicated in patients under 18 years of age. Hypereosinophilic Syndrome: NUCALA is not indicated