Merck's Oral PCSK9 Inhibitor Shows Promise in Phase III Trials, Positioning Company as Leader in Cholesterol Treatment Innovation

Merck & Co. has taken a significant step forward in its bid to bring the first oral PCSK9 inhibitor to market, with its experimental drug enlicitide decanoate demonstrating positive results in two pivotal Phase III trials. The studies, part of the company's extensive CORALreef development program, showed that the drug effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in patients with high cholesterol, potentially opening up a new frontier in cardiovascular disease treatment.

Phase III Trial Results Demonstrate Efficacy and Safety

The CORALreef HeFH study, which enrolled adults with heterozygous familial hypercholesterolemia (HeFH) and a history of or risk for atherosclerotic cardiovascular disease, met its primary endpoint. Enlicitide decanoate showed statistically significant and clinically meaningful reductions in LDL-C levels at Week 24 compared to placebo in patients already being treated with statins.

Similarly, the CORALreef AddOn trial, focusing on patients with hypercholesterolemia, demonstrated the drug's superiority over existing oral non-statin agents. Enlicitide decanoate achieved its key endpoint of reducing LDL-C levels at Week 8 compared to ezetimibe and bempedoic acid.

Importantly, both studies reported no clinically meaningful differences in the incidence of adverse events between treatment arms, suggesting a favorable safety profile for the drug.

Market Implications and Competitive Landscape

If approved, enlicitide decanoate would become the first oral PCSK9 inhibitor available to patients, potentially transforming the cholesterol treatment landscape. The current market is dominated by injectable PCSK9 inhibitors such as Amgen's Repatha and Sanofi-Regeneron's Praluent, which have faced challenges in market adoption due to administration route and reimbursement issues.

Merck's oral formulation could address these barriers, with CEO Robert Davis suggesting that the company's investment in production capabilities may allow for competitive pricing. This strategy could help avoid the reimbursement challenges faced by injectable PCSK9 inhibitors.

The success of enlicitide decanoate is crucial for Merck's future growth, especially as the company prepares for the patent expiration of its blockbuster cancer drug Keytruda later this decade. BMO Capital Markets analysts have described the drug as a "multi-billion dollar opportunity" that could expand the PCSK9 market beyond current injectable therapies.

However, Merck is not alone in this race. AstraZeneca is developing its own oral PCSK9 inhibitor, AZD0780, which has shown promising results in Phase II trials. The competition between these two pharmaceutical giants will likely intensify as they vie for market dominance in oral PCSK9 inhibition.