PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrBENLYSTA Belimumab for injection 120 mg in 5 mL vial lyophilized powder for intravenous infusion 400 mg in 20 mL vial lyophilized powder for intravenous infusion Belimumab injection 200 mg in 1 mL for subcutaneous injection Selective Immunosuppressant GlaxoSmithKline Inc. 7333 Mississauga Road Mississauga, Ontario L5N 6L4 Date of Initial Authorization: JUL 06, 2011 Date of Revision: JUL 29, 2021 Submission Control Number: 243390 ©2021 GSK group of companies or its licensor Trademarks are owned by or licensed to the GSK group of companies July 29,2021 BENLYSTA, Belimumab Page 1 of 68 RECENT MAJOR LABEL CHANGES 1 INDICATIONS 07/2021 4 DOSAGE AND ADMINISTRATION, 4.2 RECOMMENDED DOSE 07/2021 AND DOSAGE ADJUSTMENT 4 DOSAGE AND ADMINISTRATION, 4.4 ADMINISTRATION 07/2021 7 WARNINGS AND PRECAUTIONS 07/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ........................................................................................... 2 TABLE OF CONTENTS ............................................................................................................. 2 1 INDICATIONS.............................................................................................................. 4 1.1 Pediatrics .................................................................................................... 4 1.2 Geriatrics .................................................................................................... 4 2 CONTRAINDICATIONS................................................................................................. 4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 4 4 DOSAGE AND ADMINISTRATION................................................................................. 5 4.1 Dosing Considerations .................................................................................................. 5 4.2 Recommended Dose and Dosage Adjustment ............................................................. 5 4.3 Reconstitution .................................................................................................... 6 4.4 Administration .................................................................................................... 7 4.5 Missed Dose .................................................................................................... 8 5 OVERDOSAGE............................................................................................................. 8 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 8 7 WARNINGS AND PRECAUTIONS................................................................................ 10 7.1 Special Populations .................................................................................................. 12 7.1.1 Pregnant Women .................................................................................................. 12 7.1.2 Breast-feeding .................................................................................................. 13 7.1.3 Pediatrics .................................................................................................. 13 7.1.4 Geriatrics .................................................................................................. 13 July 29,2021 BENLYSTA, Belimumab Page 2 of 68 8 ADVERSE REACTIONS................................................................................................ 13 8.1 Adverse Reaction Overview........................................................................................ 13 8.2 Clinical Trial Adverse Reactions .................................................................................. 14 8.3 Less Common Clinical Trial Adverse Reactions........................................................... 19 8.5 Post-Market Adverse Reactions.................................................................................. 19 9 DRUG INTERACTIONS ............................................................................................... 19 9.2 Drug Interactions Overview ........................................................................................ 19 10 CLINICAL PHARMACOLOGY....................................................................................... 20 10.1 Mechanism of Action ................................................................................................ 20 10.2 Pharmacodynamics .................................................................................................. 20 10.3 Pharmacokinetics .................................................................................................. 20 11 STORAGE, STABILITY AND DISPOSAL......................................................................... 23 12 SPECIAL HANDLING INSTRUCTIONS........................................................................... 24 PART II: SCIENTIFIC INFORMATION ...................................................................................... 25 13 PHARMACEUTICAL INFORMATION ........................................................................... 25 14 CLINICAL TRIALS ....................................................................................................... 26 14.1 Trial Design and Study Demographics ...................................................................... 26 14.2 Study Results .................................................................................................. 32 15 MICROBIOLOGY ....................................................................................................... 41 16 NON-CLINICAL TOXICOLOGY..................................................................................... 42 PATIENT MEDICATION INFORMATION - Intravenous............................................................ 47 PATIENT MEDICATION INFORMATION - Autoinjector ........................................................... 54 INSTRUCTIONS FOR USE – Autoinjector ............................................................................... 62 July 29,2021 BENLYSTA, Belimumab Page 3 of 68 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS BENLYSTA (belimumab for injection, belimumab injection) is indicated in addition to standard therapy for: reducing disease activity in adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE). treatment of active lupus nephritis in adult patients. The safety and efficacy of BENLYSTA have not been evaluated in patients with severe active central nervous system lupus. The efficacy of BENLYSTA in SLE patients of Black African heritage has not been clearly established. 1.1 Pediatrics No data were made available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. 1.2 Geriatrics Although data are limited, dosage adjustment is not recommended in patients > 65 years of age (see 10.3 Pharmacokinetics). 2 CONTRAINDICATIONS BENLYSTA is contraindicated in patients who are hypersensitive to belimumab (e.g., have demonstrated anaphylaxis) or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Infusion/Injection-Related Systemic Reactions and Hypersensitivity, including Anaphylaxis Administration of BENLYSTA may result in infusion or injection-related systemic reactions and hypersensitivity reactions, which can be severe or fatal. Serious infusion reactions and serious anaphylaxis/hypersensitivity have been observed uncommonly (see 7 WARNINGS AND PRECAUTIONS, General, Infusion/Injection-Related Systemic Reactions and Hypersensitivity). Severe and sometimes fatal Infections, including Progressive Multifocal Leukoencephalopathy (PML) Severe infections, including PML have been reported in patients receiving BENLYSTA, and other immune-modulating therapies for the treatment of SLE. Some cases were fatal (see 7 WARNINGS AND PRECAUTIONS, Immune, and 8 ADVERSE REACTIONS, Infections, and 8.5 Post-Market Adverse Drug Reactions). Psychiatric Disorders: Depression and suicidality have been reported in trials with BENLYSTA. Patients should be instructed to contact their healthcare provider if they experience new or worsening July 29,2021 BENLYSTA, Belimumab Page 4 of 68 depression, or suicidal thoughts/behaviour (See 7 WARNINGS AND PRECAUTIONS, Psychiatric, and 8 ADVERSE REACTIONS, Clinical Trial Adverse Reactions, Psychiatric Disorders). 4 DOSAGE AND ADMINISTRATION Where instructions are specific to either the intravenous infusion or subcutaneous injection, this administration route is specifically named under each subheading below. 4.1 Dosing Considerations Discontinuation of treatment with BENLYSTA in SLE should be considered if there is no improvement in disease control after 6 months of treatment. In active lupus nephritis, BENLYSTA should be used in combination with corticosteroids and mycophenolate or cyclophosphamide for induction, or mycophenolate or azathioprine for maintenance. The patient’s condition should be evaluated continuously. 4.2 Recommended Dose and Dosage Adjustment Intravenous Administration SLE or lupus nephritis The recommended dosage regimen is 10 mg/kg at 2-week intervals for the first three doses and at 4- week intervals thereafter. BENLYSTA should