Regulatory Decision Summary for Kevzara

This Supplement to a New Drug Submission (SNDS) was filed for Kevzara (sarilumab injection) for a new indication for use in polymyalgia rheumatica (PMR) patients who have had an inadequate response to corticosteroids (CS) or who cannot tolerate CS taper. In support, the sponsor submitted one pivotal trial SAPHYR (EFC15160) and a real-world effectiveness (RWE) study (CS-00737). The sponsor also provided a supportive study (EFC15068) in a related condition (giant cell arteritis) to support the safety assessment. Upon review of the submitted data package, Health Canada authorized Kevzara for the following indication: Kevzara (sarilumab injection) is indicated for treatment of adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids, or who have experienced relapse during corticosteroid taper.

Kevzara (sarilumab injection) is currently approved for use in treating rheumatoid arthritis (RA). In this Supplement to a New Drug Submission (SNDS), the sponsor proposed a new indication, treatment of polymyalgia rheumatica (PMR). To support the evaluation of efficacy and safety of sarilumab for this condition, the sponsor provided a single pivotal study, SAPHYR (EFC15160), supplemented by real-world evidence study (CS-00737) and sarilumab safety findings in related populations (a placebo-controlled study in patients with giant cell arteritis (EFC15068) and an integrated summary of safety findings from the RA studies with Kevzara).

The pivotal study SAPHYR (EFC15160) was a 52-week, multicentre, randomized, double-blind, placebo-controlled Phase 3 study. One hundred and eighteen participants with PMR were randomized in a 1:1 ratio to two parallel arms: Group 1 was treated with sarilumab 200 mg every two weeks with a 14-week corticosteroid taper, and Group 2 was treated with matching placebo with a 52 week corticosteroid taper. On the primary efficacy endpoint, the proportion of patients achieving sustained remission at Week 52, 17 participants (28.3%) in the sarilumab + 14 week taper group and 6 participants (10.3%) in placebo + 52 week taper achieved sustained remission. The proportion difference for sarilumab vs. placebo was 18.0 (95% confidence interval [CI]: 4.15, 31.82; p-value 0.0193), which was statistically significant. On the key secondary efficacy endpoint, cumulative corticosteroid dose during the treatment period, was statistically significant, and other secondary endpoints, including each of the individual components of the composite primary endpoint, trended in support of the primary. While uncertainty remains with regard to the potential interaction between different corticosteroid taper regimen and sarilumab, due to the design of the study, the efficacy findings nevertheless suggested that sarilumab can improve some clinically relevant outcomes.  

The safety profile of sarilumab in PMR patients, based on the pivotal study SAPHYR (EFC15160), was consistent with the known safety profile of sarilumab in RA. However, as there is limited data in PMR patients, the sponsor is planning a post-approval study further investigating the safety of sarilumab in patients with PMR.

Overall, the benefit-risk profile was favourable for Kevzara 200 mg for adult patients with PMR who have had an inadequate response to corticosteroids or who have experienced relapse during corticosteroid taper when used under the conditions of use recommended in the approved Product Monograph.

An updated Kevzara European Union (EU) Risk Management Plan (RMP) (version 4.0) and the Canadian RMP Addendum (version 5) was reviewed by Health Canada and considered acceptable. No further RMP-related follow-up is warranted.

Revisions made to the Kevzara package inserts met all applicable regulations and guidance.

A Notice of Compliance (NOC) was recommended.

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