Wegovy (semaglutide): NDA 215256

Dr. Mohamadi reviewed and recommends approval of the final carton and container labeling, agreed upon with the applicant.

In summary, Dr. Ramaswamy and the individual discipline reviewers all support approval of the application, and I concur with their recommendations.

The CDRH reviewer, Dr. Dunya Karimi, reviewed the device component of the combination product and recommends approval.

The FDA clinical pharmacology review team recommends approval, and I concur with the recommendation.

Both Dr. Golden and Dr. Song recommend approval of semaglutide as an adjunct to a reduced calorie diet and exercise for chronic weight management in the proposed population.

This application includes substantial evidence of effectiveness that semaglutide 2.4 mg injection, administered subcutaneously once weekly, results in clinically meaningful weight loss and improvement in anthropomorphic and cardiometabolic parameters in patients with obesity or overweight.

The three randomized, placebo controlled, Phase 3 clinical trial results represent substantial evidence of effectiveness that semaglutide 2.4 mg injection, administered subcutaneously once weekly results in clinically meaningful weight loss and improvement in anthropomorphic and cardiometabolic parameters in patients with obesity and overweight, with and without type 2 diabetes.

Treatment with semaglutide 2.4 mg weekly resulted in statistically significant and clinically meaningful weight loss compared to placebo.

A stopping rule recommending discontinuation of semaglutide in patients who fail to achieve the target dose following the recommended escalation schedule is appropriate, as the Phase 3 trials were not designed to demonstrate substantial evidence of effectiveness at any other dose level.

The estimated effect size between continued treatment and withdrawal to placebo was clinically meaningful and statistically robust.

The total number of patients experiencing a component of the primary MACE endpoint was 108 (6.6%) in the semaglutide arms and 146 (8.9%) in the placebo arm.

Conduct a medullary thyroid carcinoma registry-based case series of at least 15 years duration to systematically monitor the annual incidence of medullary thyroid carcinoma in the United States and to identify any increase related to the introduction of semaglutide for the treatment of obesity into the marketplace.

Acute gallbladder disease is a labeled warning (Section 5) in the Saxenda and Victoza labels.

By contrast, cholelithiasis is reported as an adverse reaction only (Section 6) in the semaglutide for diabetes labels.

A REMS is not considered necessary for this application.

Most common adverse reactions (incidence >= 5%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis (6.1).

Cholecystitis was reported by 0.8% of WEGOVY-treated pediatric patients and 0% placebo-treated patients [see Adverse Reactions (6.1)].

If required postmarketing clinical trials fail to verify clinical benefit or are not conducted with due diligence, including with respect to the conditions set forth below, we may withdraw this approval.

The assay development PMC (3294-3) as well as a PMC to "conduct a study to assess the incidence of neutralizing antibodies to semaglutide and GLP-1 in subjects treated with semaglutide using the assays developed in 3294-3" (PMC 32944) were therefore released.

Novo Nordisk Inc. submitted an efficacy supplement S-011 to NDA 215256 Wegovy® SC injection on 09/08/2023 to fulfill PMR 4081-6 and to evaluate the long-term effects of semaglutide.