Bagsværd, Denmark: As Novo Nordisk’s injectable diabetes-obesity duo Ozempic and Wegovy grab all the limelight, an oral version of the semaglutide drug showed it can provide heart-related benefits, too.
Oral semaglutide, sold as Rybelsus®, reduced the risk of a group of cardiovascular events by 14% compared with placebo in certain patients with Type 2 diabetes in a late-stage study, Novo said Monday.
Rybelsus® is approved as a diabetes treatment, and the study, coded SOUL, tested the oral GLP-1 drug in patients with Type 2 diabetes and established cardiovascular disease with or without chronic kidney disease. The 9,650 patients enrolled in the trial received either Rybelsus or placebo, both as an adjunct therapy on top of standard of care.
The group of cardiovascular events by which Rybelsus was measured, called MACE, included cardiovascular-related death, nonfatal myocardial infraction or stroke. All three types of events contributed to the overall risk reduction, Novo said. The 14% improvement was statistically significant, and the SOUL trial has met its primary goal, the company said.
Armed with the positive phase 3 readout, Novo plans to file Rybelsus for cardiovascular outcomes approvals in the U.S. and Europe “around the turn of the year.” The detailed SOUL results will be presented at an upcoming medical meeting.
“Approximately one in three adults with type 2 diabetes also have cardiovascular disease; therefore, it is crucial to have therapies that can address both conditions,” Martin Holst Lange, M.D., Ph.D., Novo’s head of development, said in a statement Monday.
Rybelsus’ cardiovascular outcomes showing was not a surprise. Its injectable counterpart, Ozempic, in 2020 won an FDA approval to reduce the risk of cardiovascular-related events in Type 2 diabetes patients who have known heart disease. In the SUSTAIN 6 trial, Ozempic cut the risk of MACE by 26% versus placebo; both trial arms included standard of care.
Semaglutide has demonstrated heart benefits in various treatment settings. In the phase 3 SELECT trial, the FDA-approved obesity treatment Wegovy reduced the risk of MACE by 20% in nondiabetic adults who are overweight or obese and who have a history of heart disease. In March, the FDA blessed the drug with a new approval based on those results.
Novo also hopes to add reducing heart failure and related symptoms to Wegovy’s label, even though the Danish company previously pulled an application in that setting.
Novo conducted two phase 3 trials dedicated to heart failure with preserved ejection fraction (HFpEF). But the FDA indicated that “the likelihood of getting hard endpoints into the U.S. label would increase” if Novo can gather a larger volume of data with more HFpEF-related events, Lange explained on an investor call in August. The company later that month shared a pooled HFpEF analysis of semaglutide from four clinical trials, including SELECT and a kidney outcomes study called FLOW.
Initially approved by the FDA in 2019 as the first oral GLP-1 med, Rybelsus generated first-half 2024 sales of 10.9 billion Danish kroner ($1.6 billion). That compared with Ozempic’s 56.7 billion kroner ($8.25 billion) and Wegovy’s 21 billion kroner ($3.05 billion) for the same period.
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