Novo Nordisk Receives FDA Refusal to File Letter for Semaglutide 2.0 mg Label Expansion in Type 2 Diabetes

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On March 22, Novo Nordisk announced that it had received a Refuse-to-File (RFL) letter from the U.S. Food and Drug Administration (FDA) regarding its supplemental New Drug Application (sNDA) to expand the label of once-weekly semaglutide 2.0 mg for the treatment of type 2 diabetes. The FDA issues an RFL letter when it determines that additional information is required to review a complete application.

In this RFL, the FDA requested additional information, including data related to the proposed new manufacturing site. Although more information is required for the resubmission, Novo Nordisk stated that it believes the completed clinical trial program is sufficient to support the label expansion application for semaglutide. Novo Nordisk also indicated that it expects to resubmit the application to the FDA in the second quarter of 2021.

On January 20 this year, Novo Nordisk submitted a label expansion application to the FDA to include a new 2.0 mg dose in the existing marketing authorization for the glucose-lowering drug Ozempic (semaglutide). Ozempic is a once-weekly subcutaneous injection of a glucagon-like peptide-1 (GLP-1) analog. In the United States, it has been approved at doses of 0.5 mg and 1.0 mg for the treatment of adult patients with type 2 diabetes, as well as to reduce the risk of major adverse cardiovascular events in adult patients with type 2 diabetes and established cardiovascular disease. On December 29, 2020, the company also submitted the same label expansion application to the European Medicines Agency.

Application for Label Expansion of Semaglutide 2.0 mg, Based on Results from the SUSTAIN FORTE Trial within the SUSTAIN Clinical Program. This was a 40-week Phase 3b efficacy and safety trial evaluating once-weekly subcutaneous semaglutide 2.0 mg versus semaglutide 1.0 mg as an add-on to metformin and/or sulfonylureas in 961 adult patients with type 2 diabetes requiring intensified treatment. The primary endpoint was the reduction in glycated hemoglobin (HbA1c) levels at Week 40.

The results demonstrated that the study met its primary endpoint: at Week 40, using two evaluation methods, the reduction in HbA1c in the 2.0 mg treatment group was both statistically significant and superior compared with the 1.0 mg treatment group. Furthermore, the 2.0 mg treatment group showed superiority over the 1.0 mg treatment group in terms of weight loss. In this trial, both doses of semaglutide were shown to be safe and well tolerated. The most common adverse reactions were gastrointestinal events, which were predominantly mild to moderate in severity, decreased over time, and were consistent with the profile of the GLP-1 receptor agonist class. The incidence of gastrointestinal adverse events was similar between the 1.0 mg and 2.0 mg groups in this trial.

The SUSTAIN clinical program is evaluating once-weekly subcutaneous semaglutide. The program currently comprises 11 Phase 3 global clinical trials, including one cardiovascular outcomes trial involving more than 11,000 adult patients with type 2 diabetes.

Reference Source:

1.Novo Nordisk receives Refusal to File letter for once-weekly semaglutide 2.0 mg for the treatment of type 2 diabetes

2.Once-weekly semaglutide 2.0 mg demonstrates superior reduction in HbA1c vs once-weekly semaglutide 1.0 mg in people with type 2 diabetes in the SUSTAIN FORTE trial