Regulatory Decision Summary for Wegovy

The purpose of this Supplement to a New Drug Submission (SNDS) was to expand the indication for Wegovy to include the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

Based on the review of the data provided in the SNDS, Health Canada issued a Notice of Compliance with Conditions - Qualifying Notice (NOC/c-QN) on November 21, 2025. In their response to the NOC/c-QN, the sponsor provided an “Agreement Letter” and a “Letter of Undertaking” on November 28, 2025 which were both considered acceptable.

The efficacy of semaglutide 2.4 mg for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) was supported by one ongoing Phase 3a trial (NN9931-4553 ESSENCE – pivotal trial) and two completed Phase 2 trials (NN9931-4296 and NN9931-4492). The ESSENCE trial is a randomized, multicenter, double-blind, parallel-group trial comparing weekly subcutaneous (s.c.) injection of semaglutide 2.4 mg and placebo in subjects with MASH and stage F2 or F3 fibrosis. The trial includes two parts: Part 1 is complete and Part 2 is ongoing. The total trial duration (Parts 1 and 2) will be approximately 261 weeks (~ five years) and is expected to be completed in 2029.

In Part 1 of the ESSENCE trial, the co-primary endpoints were surrogate histology endpoints evaluated at week 72, namely (1) resolution of steatohepatitis and no worsening of liver fibrosis, and (2) improvement in liver fibrosis and no worsening of steatohepatitis. Data from the ESSENCE trial Part 1 demonstrated superiority of semaglutide 2.4 mg over placebo in both co-primary endpoints in subjects with baseline stages F2 or F3 fibrosis. The secondary endpoints, resolution of steatohepatitis combined with improvement in liver fibrosis and change from baseline in body weight, supported the conclusions from the co-primary endpoints.

Although promising benefits have been observed in histological markers in Part 1 of the ESSENCE trial, uncertainty remains due to the lack of established guidance on the minimum treatment effect considered clinically meaningful and likely to translate into long-term benefits. These long-term benefits include the prevention of hard outcomes such as liver transplantation, decompensation events of liver cirrhosis, and death. Studying MASH to draw conclusions about long-term outcomes within a reasonable timeframe is particularly challenging, given the slow progression of the disease. Part 2 of the trial, which includes a five-year follow-up period, is designed to confirm these findings by assessing the overall clinical impact of semaglutide 2.4 mg in this patient population.

The safety profile of semaglutide 2.4 mg patients with MASH and stage F2 or F3 fibrosis was consistent with previous findings from clinical trials and post-marketing data from other indications.

The global Risk Management Plan (RMP) for Wegovy (semaglutide injection) was submitted to Health Canada as part of the Supplemental New Drug Submission (SNDS; Control # 296143). The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP is considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures for Wegovy. This includes providing information in the product monograph and identifying populations and areas where more data are needed. Results related to the safety and effectiveness of Wegovy from ongoing and planned studies will be submitted in Periodic Safety Update Reports (PSURs) as they become available.

The labelling material submitted met all applicable regulations and guidance.

Based on the promising evidence observed on the histological markers, a Notice of Compliance with Conditions (NOC/c) was issued. 

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