Regulatory Decision Summary for Ozempic

Market authorization was sought for Ozempic at a higher maintenance dose of 2 mg once weekly, in a pre-filled syringe at a higher strength. The device was unchanged from the authorized presentation but the strength of product was doubled. The Sponsor proposed a multiple bridging approach to support this authorization and confirmed that direct clinical data will be generated from an upcoming study. This approach was deemed acceptable.

In the double blind study SUSTAIN FORTE, 961 patients inadequately controlled with metformin with or without sulfonylurea were randomised to semaglutide 1 mg once weekly or semaglutide 2 mg once weekly for 40 weeks. Patients had a mean age of 58 years and a mean duration of type 2 diabetes of 9.5 years. Mean body mass index (BMI) was 34.6 kg/m².

The study achieved its primary objective. The estimated mean HbA_1c difference in reduction from baseline to Week 40 was -0.18%-point favouring the semaglutide 2 mg dose. This difference is clinically meaningful and statistically significant based on either the treatment or the hypothetical estimand strategies.

Secondary confirmatory efficacy endpoints, such as change from baseline at Week 40 in body weight, superiority of semaglutide 2 mg and reduction in fasting plasma glucose, were consistent with the observed reduction in HbA_1c. A greater proportion of subjects achieved HbA_1c target levels at Week 40 with semaglutide 2 mg compared to semaglutide 1 mg, as evaluated by the treatment policy estimand (64.4% vs 55.8% for HbA_1c <7%; 49.4% vs 37.1% for HbA_1c <6.5%). This difference was clinically meaningful. In general, HbA_1c results were similar across pre-specified subgroups.

Once weekly semaglutide 2 mg was safe and well tolerated in subjects with type 2 diabetes. The safety and tolerability profile of semaglutide 2 mg was comparable to that of semaglutide 1 mg seen in the previous phase 3a trials and consistent with the known safety profile of the GLP-1 RA drug class.

At Week 40, 959 patients had been exposed to semaglutide 1 mg or 2 mg. Gastrointestinal disorders were reported in a slightly greater proportion of patients exposed to semaglutide 2 mg (34.0%) compared to semaglutide 1 mg (30.8%). The gastrointestinal adverse reactions led to treatment discontinuation in similar proportions in the semaglutide 1 mg (2.7 %) and 2 mg (3.3 %) treatment groups.

The rates of treatment emergent severe or blood glucose-confirmed symptomatic hypoglycemia episodes from first dose to Week 40 were low and comparable in the two arms. The proportion of subjects with adverse events (AE) related to cardiovascular disorders was comparable in the two arms (5.0% vs. 4.0%). In both treatment groups, mean levels of lipase increased by 30% and amylase increased by 20%, but there were no AEs related to pancreatitis.

Serious adverse events (SAE) were reported by comparable proportions of subjects and with a comparable event rate across the two treatment arms (4.4% vs 5.2%). There were 3 deaths reported, 2 in the semaglutide 2 mg arm and 1 in the semaglutide 1 mg arm.

Overall, the benefits of Ozempic 2 mg outweigh the risks in the target patient population. The benefit-risk profile of Ozempic continues to be acceptable for the sought indication.

An updated Risk Management Plan (RMP) for Ozempic was reviewed by Health Canada and considered acceptable.

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