Regulatory Decision Summary for Ozempic

Ozempic (semaglutide injection) is a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of drug that is already marketed by this and other Sponsors for the purpose of treatment of Type 2 Diabetes mellitus. Ozempic is administered once weekly to improve glycemic control.

Management of T2D involves controlling serum glucose and minimizing side effects such as body weight gain and hypoglycemia. Due to the progressive nature of the disease, many patients require combining multiple anti-hyperglycemic agents to control their disease and/or minimize side effects.

Benefits
This NDS provided data from 5 pivotal trials with primary endpoints of reduction in hemoglobin A_1c (HbA_1c, a marker of long term glycemic control) from baseline compared to placebo or comparators, and administered with other antidiabetic drugs or as monotherapy. Ozempic provided significant improvements in HbA_1c over placebo and each comparator (insulin glargine, exenatide, sitagliptin). The Sponsor included a cardiovascular outcomes trial (CVOT) which showed no increase in major adverse cardiac events (MACE) risk with long-term treatment with Ozempic.

Risks
Subjects that received Ozempic had more adverse events than placebo-treated subjects but similar incidence to comparator drugs. However, Ozempic-treated subjects had significantly more gastrointestinal-related adverse events, and in many cases this was the cause of early discontinuation from trials. In the CVOT, there was a concerning finding indicating significantly increased incidence of diabetic retinopathy complications in Ozempic subjects. Given the lack of similar findings in other pivotal trials, labelling was updated to include these findings. In subjects that were also receiving sulfonylurea or basal insulin in addition to Ozempic, hypoglycemic events were more common. In terms of known risks associated with the GLP-1 receptor agonist drug class, the Ozempic clinical program did not demonstrate increased risk of pancreatitis or malignancies (including medullary thyroid carcinoma).

Benefit/Risk Assessment
Overall, the benefits of Ozempic as an add-on treatment for glycemic control in adult T2D patients outweigh the risks when adequate labelling and risk management plans are implemented to address the safety concerns noted above.