The applications seek FDA approval for blood sugar control and cardiovascular risk reduction in adults with type 2 diabetes.
Novo Nordisk has submitted 2 New Drug Applications (NDAs) to the US Food and Drug Administration (FDA) for oral semaglutide. One application is for approval as a supplement to diet and exercise to improve blood sugar in adults with type 2 diabetes (T2D). The second application is for an indication to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or death in adults with T2D and established cardiovascular disease.
The first application was submitted along with a Priority Review voucher for an anticipated review timeline of 6 months. The MACE reduction application has an anticipated 10-month timeline for review.
Additionally, a supplemental NDA (sNDA) was submitted for semaglutide injection 0.5 mg or 1 mg (Ozempic). The sNDA seeks approval for an indication to reduce the risk of MACE such as heart attack, stroke, or death in adults with type 2 diabetes and established CVD. Semaglutide injection was initially approved by the FDA in December 2017 an adjunct glycemic control therapy in adults with T2D.
The company is “very excited” about the 3 applications, said Todd Hobbs, MD, vice president and US chief medical officer of Novo Nordisk. "We know that many adults with type 2 diabetes are still struggling to control their blood sugar and are at increased cardiovascular risk. We hope that, if approved, these products can help those patients," added Hobbs in a statement.
The oral semaglutide applications are supported by data from 10 PIONEER clinical trials that compared the GLP-1 receptor agonist to sitagliptin, empagliflozin, liraglutide, and placebo. The PIONEER trial program involved 9543 adult patients with type 2 diabetes.
Two cardiovascular outcomes trials support the applications for injection and oral semaglutide for cardiovascular risk reduction—SUSTAIN 6 and PIONEER 6, respectively.
SUSTAIN 6 was a randomized, double-blinded, placebo-controlled trial that evaluated the CV safety of semaglutide injection added to standard of care compared to placebo. The study included 3297 patients with T2D and either established cardiovascular disease or high risk of cardiovascular events.
PIONEER 6 was similarly randomized, double-blinded, and placebo-controlled, and compared oral semaglutide alongside standard of care to placebo. The trial, which included 3138 participants, demonstrated non-inferiority to placebo with regard to MACE outcomes.
The MACE composite had a hazard ratio (HR) of .79 in favor of oral semaglutide, reaching non-inferiority. However, the reduction of MACE with oral semaglutide did not reach statistical significance.