Headline results from the SOUL cardiovascular outcomes trial show the trial achieved its primary objective by demonstrating a statistically significant and superior reduction in major adverse cardiovascular events (MACE) of 14% for people treated with oral semaglutide compared to placebo (based on treatment policy estimand: treatment effect regardless of treatment adherence). In the trial, oral semaglutide appeared to have a safe and well-tolerated profile in line with previous oral semaglutide trials.
The primary endpoint of the study was defined as the composite outcome of the first occurrence of MACE defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. All three components of the primary endpoint contributed to the superior MACE reduction demonstrated by oral semaglutide.
SOUL was a multicentre, international, randomised, double-blind, parallel-group, placebo-controlled, phase 3 cardiovascular outcomes trial with 9,650 patients with type 2 diabetes and established cardiovascular disease (CVD) and/or chronic kidney disease (CKD). As part of standard of care, 49% of patients received SGLT2i at some point during the trial. The SOUL trial was initiated in 2019.
The key objective of SOUL was to demonstrate that oral semaglutide lowers the risk of major adverse cardiovascular events (a composite endpoint consisting of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) compared to placebo, both added to standard of care in patients with type 2 diabetes and established CVD and/or CKD.
Oral semaglutide is administered once daily and is approved for use in three doses, 3 mg, 7mg and 14 mg, under the brand name Rybelsus. It is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise.
"We are pleased to see that the results from SOUL demonstrate that oral semaglutide reduces the risk of cardiovascular events and that the benefits of oral semaglutide come on top of standard of care,” said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. “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.”
Novo Nordisk expects to file for regulatory approval of a label expansion for Rybelsus in both the US and EU around the turn of the year. The detailed results from SOUL will be presented at a scientific conference in 2025.
In the EU, a new formulation of 1.5 mg, 4 mg and 9 mg doses of Rybelsus are approved and are bioequivalent to the original formulation of Rybelsus.
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