Regulatory Decision Summary for Upgolyv

The purpose of this New Drug Submission (NDS) is to seek market authorization of Upgolyv (golimumab) solution for subcutaneous (SC) injection (100 mg/1.0 mL and 50 mg/0.5mL autoinjector and single-use pre-filled syringe solution) as a biosimilar biologic drug to the reference biologic drug Simponi (golimumab injection), marketed by Janssen Inc. Simponi has been authorized in Canada since April 2009. This is the first biosimilar for this product on the Canadian market.

The reference biologic drug, Simponi, is available in pre-filled syringe (PFS) presentation at 50 mg/0.5 mL and 100 mg/1.0 mL strength for SC injection. Simponi I.V. is available in vial presentation at 50 mg/4.0 mL strength for intravenous (IV) infusion.

The sponsor for Upgolyv, JAMP Pharma Corporation, is seeking approval for all adult SC indications held by the reference biologic drug Simponi. Approval of the Simponi IV vial presentation is not being sought in this submission.

Upgolyv (golimumab) is a biosimilar biologic drug to the Canadian Reference Biologic Drug (CRBD) Simponi. The Sponsor sought all indications for the SC presentation of the CRBD on the basis of biosimilarity.

The clinical studies submitted in the dossier were a Phase 1 comparative bioavailability study (Study AVT05-GL-P01) and a Phase 3 study (Study AVT05-GL-C01). In both studies, European Union (EU)-Simponi was nominated as the reference biologic drug. United States (US)-Licensed Simponi was considered supportive in the Phase 1 study.

Study AVT05-GL-P01 was a Phase 1, randomized, double-blind, 3-arm, parallel group, single-dose study to compare the pharmacokinetics and safety of single-dose subcutaneous injection of 50 mg golimumab (Upgolyv, EU-Simponi, and US-Simponi) in healthy subjects. Each subject was randomised in a 1:1:1 ratio to receive a single 50 mg subcutaneous injection of either Upgolyv, EU- or US-Simponi.

The comparative bioavailability study demonstrated pharmacokinetic comparability between Upgolyv and EU-Simponi. The point estimate for Upgolyv and EU-Simponi geometric least square mean ratio for the maximum concentration (C_max) and the 90% confidence intervals (CI) for the area under the concentration versus time curve to the time of the last quantifiable concentration (AUC_0-last) were within the Health Canada specified comparability margins of 80.0% to 125.0%.

Study AVT05-GL-C01 was a randomized, active-controlled, double-blind study to compare efficacy, pharmacokinetics, safety and immunogenicity of subcutaneous injection of Upgolyv or EU-Simponi at dose of 50 mg at baseline, and every 4 weeks thereafter, in patients with moderate to severe Rheumatoid Arthritis up to 48 weeks. The primary efficacy endpoint was the change from baseline as measured by disease activity score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) at Week 16. The 95% CI of the change from baseline in the DAS28-CRP at week 16 between Upglyv and EU-Simponi was contained within the equivalence margin of (-0.6, 0.6).

No imbalance in safety profile was observed between Upgolyv and EU-Simponi and consistent C_trough exposures were observed following multiple dosing. No consistent imbalances in immunogenicity were observed between Upgolyv and EU-Simponi.

The pharmacokinetic, efficacy, and safety results evaluated in this submission provided sufficient clinical support for the establishment of biosimilarity between Upgolyv and the CRBD Simponi.

Overall, the benefit-risk profile was favorable for Upgolyv (50 mg/0.5 mL and 100 mg/1 mL autoinjector and single-use pre-filled syringe solution) for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

An updated Risk Manaement plan (RMP) for Upgolyv was submitted as part of this NDS. Based on the information reviewed by Health Canada, the Upgolyv RMP aligned with that of the reference biologic drug Simponi, and was considered acceptable. There are no additional pharmacovigilance activities other than routine pharmacovigilance, planned for Upgolyv. However, as required, emergent post-approval safety information will be submitted in Periodic Benefit-Risk Evaluation Reports.

The chemistry and manufacturing information submitted for Upgolyv has demonstrated that the drug substance and drug product have been well-characterized and can be consistently manufactured to meet the approved specifications.

The labelling material submitted met all applicable regulations and guidance.

For further details about Upgolyv, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.