Ozempic (semaglutide): NDA 209637

Overall, Dr. He concludes that the applicant has provided substantial evidence that both doses of semaglutide are effective in improving glycemic control.

The maintenance treatment period was 6 months for the following efficacy trials: 3623 monootherapy vs placebo), 3625 (vs insulin glargine on a background of OADs), and 3627 (vs placebo on a background of basal insulin+metformin).

Placebo-controlled trials (trials 3623, 3627 and 3744) were doubleblinded.

Superiority of semaglutide 1 mg versus placebo in change in body weight at week 104.

The difference between semaglutide and placebo in time to first EAC-confirmed MACE among all randomized patients was analysed using a stratified Cox proportional hazards model with treatment group (semaglutide, placebo) as fixed factor.

The phase 3 trials were designed to evaluate the efficacy and safety of semaglutide in a broad population of patients with T2DM covering the continuum of T2DM care, and included five multinational trials (trials 3623, 3624, 3625, 3626, 3627), two Japanese trials (trials 4091, 4092), and a cardiovascular outcome trial (trial 3744) referred to as the CVOT.

In summary, I believe that semaglutide has a favorable benefit-risk profile.

While the nonclinical signal for MTC and the findings for pancreatitis in the semaglutide development program are similar to that of other long-acting GLP-1 RAs, REMS assessment data for other long-acting GLP-1 RA products indicate that the risk for these two concerns has been acceptably communicated to the relevant prescriber groups.

Given the REMS assessment data from other GLP-1 RA products, the DRISK and DMEP review teams believe that the risks of MTC and pancreatitis can be adequately communicated with appropriate labeling and, thus, do not recommend a REMS for semaglutide.

Overall, the semaglutide safety profile was generally consistent with the known safety profile for GLP-1 RAs, with gastrointestinal adverse events being the most common adverse events, and potential for hypoglycemia on a background of insulin and/or insulin secretagogues.

Semaglutide by itself does not appear to increase the risk for hypoglycemia, but it is expected to lead to an increased risk for hypoglycemia when used in combination with sulfonylurea or insulin.

So far, for the currently marketed GLP-1 RAs, the benefit-risk profile has not changed significantly in the post-marketing setting.

This includes 16 phase I clinical pharmacology trials, 1 phase 2 dose finding trial and 8 phase 3A therapeutic confirmatory trials.