Merck's leader in oral PCSK9 inhibitor race reduces cholesterol in pair of phase 3 trials

Merck & Co. announced positive Phase 3 results for its oral PCSK9 inhibitor candidate, enlicitide decanoate, in two trials: CORALreef HeFH, which demonstrated a statistically significant reduction in LDL-C compared to placebo, and CORALreef AddOn, which showed a significant LDL-C reduction compared to ezetimibe or bempedoic acid. These results position Merck to potentially launch the first oral PCSK9 inhibitor, offering a more convenient alternative to existing injectable treatments and potentially competing with Amgen's Repatha and Sanofi-Regeneron's Praluent; Merck shares rose 2% premarket on the news and Citi analysts anticipate approval in 2027.

Analysis

Merck & Co. has reported positive top-line results from two Phase 3 trials, CORALreef HeFH and CORALreef AddOn, for its investigational oral PCSK9 inhibitor, enlicitide decanoate. In the CORALreef HeFH study, enlicitide demonstrated a clinically meaningful reduction in baseline LDL-C levels at Week 24 compared to placebo in patients with heterozygous familial hypercholesterolemia. Similarly, the CORALreef AddOn study showed a significant LDL-C reduction at Week 8 versus approved non-statin therapies ezetimibe or bempedoic acid in hypercholesterolemia patients. While detailed data were not disclosed, Merck indicated no clinically meaningful differences in adverse event incidences. These findings position enlicitide as a potential first-in-class oral PCSK9 inhibitor, offering a daily pill alternative to current injectable treatments like Amgen's Repatha, Sanofi-Regeneron's Praluent, and Novartis' Leqvio. This development places Merck ahead of AstraZeneca, whose oral PCSK9 candidate AZD0780 showed promising Phase 2 results in March. Citi analysts view these results as encouraging, anticipating a potential U.S. approval in 2027 and highlighting enlicitide's potential to become a key player due to its oral administration and favorable efficacy/safety profile. The news prompted a 2% premarket rise in Merck's shares, underscoring investor optimism regarding enlicitide's prospects within the substantial hypercholesterolemia market.

Key Decisions for Investors

• Investors in Merck (MRK) should view these Phase 3 results as a significant positive catalyst, reinforcing the potential for a new blockbuster drug; upcoming detailed data presentations and progress towards the anticipated 2027 regulatory submission will be critical milestones to monitor.
• Holders of Amgen (AMGN), Sanofi (SNY), Regeneron (REGN), and Novartis (NVS) should assess the potential long-term competitive threat posed by an effective oral PCSK9 inhibitor, which could impact the market share of their existing injectable hypercholesterolemia treatments.
• Investors tracking AstraZeneca (AZN) should note Merck's advance, as it potentially intensifies the race to market an oral PCSK9 inhibitor and may influence the competitive landscape for AZD0780.
• Consider the broader implications for the hypercholesterolemia market, as the successful introduction of a convenient and effective oral PCSK9 inhibitor could significantly shift treatment paradigms and patient preference away from injectables.