Novo Nordisk already has broad FDA approvals in hand for its injected semaglutide products Ozempic and Wegovy to reduce the risk of cardiovascular events. Now the Danish company is hoping to score a similar nod for its under-the-radar oral version of GLP-1 treatment.
The FDA has accepted Novo’s application for a label extension for Rybelsus to reduce the risk of major adverse cardiovascular events (MACE) in adults with Type 2 diabetes who also have atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease (CKD).
It would become the first add-on indication for Rybelsus, which was originally approved for Type 2 diabetes in 2019 but has been overshadowed by the booming mainstream popularity of Ozempic and Wegovy for their weight-loss potential.
But while Ozempic and Wegovy combined for sales of 152 billion Danish kroner ($22 billion) in 2024, Rybelsus has carved a significant niche as well, generating revenue of 23.3 billion Danish kroner ($3.4 billion) last year.
In October of last year, Novo revealed that a daily 14 mg dose of Rybelsus reduced the risk of MACE by 14% versus placebo. Saturday in Chicago at the American College of Cardiology's (ACC) Annual Scientific Session and Expo, Novo presented complete results from the phase 3 SOUL trial.
In the study, which enrolled 9,650 adults with Type 2 diabetes and ASCVD and/or CKD, there were 579 patients on Rybelsus who had MACE versus 668 on placebo who experienced cardio events.
“The significant reduction in risk of composite endpoint of heart attack, stroke, or death seen in the SOUL trial in adults with type 2 diabetes highlights the cardiovascular impact of oral semaglutide,” John Buse, M.D., Ph.D., co-chair of the steering committee for the SOUL trial, said in a release.
The safety profile of Rybelsus was consistent with that seen in previous trials, and no new safety signals were observed, Novo said. Serious adverse events (SAEs) were slightly less frequent in the Rybelsus group (48%) than with placebo (50%), mostly due to the higher rate of cardio events and infections with those on placebo, the company added.
On the flip side, there was a slightly higher incidence of gastrointestinal disorders with Rybelsus (5%) as opposed to placebo (4.4%). Additionally, adverse events leading to treatment discontinuation were more common for Rybelsus (15.5%) than placebo (11.6%).
“Novo Nordisk continues to evolve its leadership beyond any one therapy area, toward a broader spectrum of cardiometabolic diseases that explores the interconnectivity of these conditions,” Michael Radin, M.D., Novo’s director of diabetes medical affairs, added in the release.
Also over the weekend at the ACC, Novo presented results from a retrospective, observational study that assessed treatment with Wegovy in patients that have cardiovascular disease and are overweight or obese.
The SCORE study showed that Wegovy was associated with a significantly lower risk of a composite of heart attack, stroke, or all-cause death by 57%. Of the 9,321 patients on Wegovy, MACE occurred in 42 (0.45%), while in the non-user group of 18,642 patients, 175 (0.95%) experienced a cardio event. Wegovy was approved in the indication last year.
Two months ago, the FDA signed off on Ozempic to reduce the risk of worsening kidney disease and cardiovascular death in those with type 2 diabetes and CKD. That nod was backed by a trial that showed Ozempic reduced risk by 24%.
In 2020, Ozempic approved to reduce risk of MACE in those with type 2 and cardiovascular disease. That endorsement was backed by a trial that showed Ozempic reduced risk by 26%.
Novo also is testing semaglutide in a range of other indications like metabolic dysfunction-associated steatohepatitis (MASH), heart failure and Alzheimer’s disease.