Regulatory Decision Summary for Wegovy

This Supplement to a New Drug Submission (SNDS) - Clinical only was filed with the purpose of expanding the indication for Wegovy to include improvement in physical function, heart failure symptoms and reduce the risk of heart failure outcomes in adults with obesity-related heart failure with preserved ejection fraction.

The efficacy data reviewed in this SNDS comprised of two phase 3 studies: STEP-HFpEF, a study conducted in patients with obesity and heart failure (HF) with preserved ejection fraction (HFpEF), and STEP-HFpEF-DM, a study in patients with obesity, type 2 diabetes (T2D) and HFpEF. A total of 529 patients were enrolled in STEP-HFpEF whereas 616 patients were enrolled in STEP-HFpEF-DM. The studies had a similar design with the dual primary endpoints of percentage change from baseline in body weight and change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS), a patient-reported outcome instrument, providing a measure of symptoms and physical limitations associated with heart failure. In both trials Wegovy demonstrated superiority over placebo on change in body weight and KCCQ-CSS, suggesting weight management control and improvement in patient-reported symptomatic HFpEF. However, the STEP-HFpEF and STEP-HFpEF- DM trials did not provide substantial evidence of a cardiovascular treatment effect, which would have required a study designed to assesses the superiority of the drug in reducing the risk of clinically meaningful cardiovascular outcomes, with primary endpoints being mortality and morbidity. Therefore, the proposed indication for HFpEF patients was rejected. However, the data suggesting an improvement in symptoms and physical limitations in patients with obesity-related HFpEF, including those with T2D, can be considered meaningful for the prescriber due to the limited treatment options for this patient population. Key study results from both trials were included in the clinical trial section of the Product Monograph (PM).

The safety profile of semaglutide observed in the STEP-HFpEF and STEP-HFpEF-DM studies was generally similar to what was previously established for Wegovy. Consistent with previous studies, subjects treated with Wegovy in the STEP-HFpEF and STEP-HFpEF-DM trials reported meaningfully higher frequencies of gastrointestinal adverse events and more events of acute kidney injury. No new serious adverse events were identified in the trials. Overall, these and other safety concerns (negative safety findings provided during review) for semaglutide have been adequately communicated in the Wegovy PM and will continue to be monitored using routine pharmacovigilance activities post-market as described in the Risk Management Plan. No additional risks were identified as part of this submission.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

The benefit-risk-uncertainty profile remains unchanged for Wegovy. Therefore, a Notice of Compliance (NOC) was recommended.

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