Novo Nordisk's oral semaglutide, Rybelsus, has demonstrated a significant 14% reduction in the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes (T2D) who also have established cardiovascular disease (CVD) and/or chronic kidney disease (CKD). This finding from the Phase III SOUL trial paves the way for a potential label expansion, positioning Rybelsus as a valuable adjunct therapy for reducing cardiovascular risk in high-risk patients. The company plans to file for regulatory approval in the US and Europe around the end of 2024 or early 2025.
The SOUL trial, a double-blind, randomized study, enrolled 9,650 participants with T2D and existing CVD and/or CKD. Patients were administered either Rybelsus or a placebo in conjunction with standard care, which included sodium-glucose cotransporter-2 inhibitors (SGLT2i) in 49% of the participants. The primary endpoint was the composite outcome of the first occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. All three components contributed to the superior MACE reduction demonstrated by oral semaglutide.
Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk, stated, "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." He also noted that approximately one in three adults with type 2 diabetes also have cardiovascular disease, making it crucial to have therapies that can address both conditions.
Rybelsus: An Oral GLP-1 Receptor Agonist
Rybelsus, a once-daily oral formulation of semaglutide, was initially approved by the FDA in 2019 for the treatment of T2D. It functions as a glucagon-like peptide-1 (GLP-1) receptor agonist, enhancing insulin secretion and reducing glucagon secretion, thereby improving glycemic control. The SOUL trial results suggest that Rybelsus offers cardiovascular benefits in addition to its established efficacy in managing blood sugar levels.
Competitive Landscape
Novo Nordisk's competitor, Eli Lilly, is also actively pursuing label expansions for its diabetes and obesity therapies. In August, Lilly presented data on retatrutide, a triple GLP-1/GIP/glucagon receptor agonist, demonstrating improved cardiac outlook and reduced serum lipids in obese or overweight patients. The market for diabetes and obesity treatments is intensely competitive, with companies vying to offer comprehensive solutions that address both glycemic control and cardiovascular risk.
Market Impact
In 2023, Rybelsus contributed DKr18.7 billion ($2.1 billion) to Novo Nordisk's sales. With the potential label expansion for cardiovascular risk reduction, GlobalData projects the therapy's sales to exceed $6.8 billion in 2030. The SOUL trial results may give Rybelsus an advantage over other oral GLP-1R agonists that are due to reach the market soon and do not have this kind of data yet.
Future Directions
Novo Nordisk plans to present detailed results from the SOUL trial at a scientific conference in 2025. Further research may explore the specific mechanisms by which Rybelsus reduces cardiovascular events and identify patient subgroups that may benefit most from this therapy.
