Merck & Co. has reported a third consecutive phase 3 clinical trial win for its oral PCSK9 inhibitor enlicitide decanoate, positioning itself as a frontrunner in the race to deliver the first oral PCSK9 treatment for hyperlipidemia. The achievement marks another milestone in the company’s CORALreef program and sets the stage for regulatory submissions.
Enlicitide Achieves Primary and Secondary Endpoints
The latest trial enrolled adults with high cholesterol who were already on stable lipid-lowering therapy, including statins, and who had either a history of major atherosclerotic cardiovascular disease (ASCVD) or were at high risk of a first event.
At 24 weeks, patients in the enlicitide arm experienced a statistically significant reduction in low-density lipoprotein cholesterol (LDL-C) compared to placebo, meeting the trial’s primary endpoint. Merck also reported positive results in several secondary endpoints, including reductions in other atherogenic lipoproteins.
A New Era for Oral PCSK9 Inhibitors
If approved, enlicitide would become the first oral PCSK9 inhibitor on the market, offering an alternative to current injectable PCSK9 therapies such as Amgen’s Repatha, Sanofi-Regeneron’s Praluent, and Novartis’ Leqvio (inclisiran).
Enlicitide is a macrocyclic peptide designed to deliver antibody-like activity in oral form, overcoming long-standing challenges in targeting the PCSK9 protein. Previous attempts at oral PCSK9 inhibitors stalled due to the lack of suitable binding sites.
Competitive Landscape: Merck vs. AstraZeneca
While Merck’s three phase 3 wins put it ahead in the oral PCSK9 race, AstraZeneca is also pursuing the space with a small-molecule PCSK9 inhibitor currently in phase 3 trials. However, Merck’s progress gives it a clear lead.
On a July earnings call, Dean Li, President of Merck Research Laboratories, emphasized that enlicitide is expected not only to be first-in-class but also best-in-class, based on data seen to date from competitors.
Looking Ahead: Cardiovascular Outcomes Trial
Merck is betting heavily on enlicitide’s potential. A large cardiovascular outcomes trial involving more than 14,500 patients is underway to determine whether enlicitide can significantly reduce the risk of major cardiovascular events. The company also sees opportunities to develop combination therapies with enlicitide to further improve lipid management.
