Merck's Oral PCSK9 Inhibitor Shows Promise in Phase 3 Trials

Merck & Co. has taken a significant step forward in the race to develop the first oral PCSK9 inhibitor, announcing positive results from two phase 3 trials for its candidate, enlicitide decanoate. The studies, part of the broader CORALreef development program, demonstrated the drug's efficacy in reducing cholesterol levels in patients with high cholesterol, potentially offering a more convenient alternative to existing injectable treatments.

Phase 3 Trial Results

The pharmaceutical giant revealed that enlicitide decanoate met its primary endpoints in two key studies. The CORALreef HeFH trial, which focused on patients with heterozygous familial hypercholesterolemia at risk of atherosclerotic cardiovascular disease, showed a clinically meaningful reduction in baseline levels of low-density lipoprotein cholesterol (LDL-C) at Week 24 compared to placebo.

Similarly, the CORALreef AddOn study, involving patients with hypercholesterolemia, demonstrated a reduction in LDL-C at Week 8 when compared to approved non-statin cholesterol medicines ezetimibe and bempedoic acid.

While specific data points were not disclosed, Merck reported that there were "no clinically meaningful differences in incidences of adverse events" in either trial, suggesting a favorable safety profile for the drug.

Market Implications and Competition

The development of an oral PCSK9 inhibitor could potentially disrupt the current hypercholesterolemia market, which is dominated by injectable treatments such as Amgen's Repatha and Sanofi-Regeneron's Praluent. Novartis' Leqvio, which uses small-interfering RNA technology to decrease PCSK9 production in the liver, is also a key player in this space.

Enlicitide's oral administration could offer a significant advantage over these existing treatments, potentially improving patient compliance and accessibility. Dean Li, M.D., Ph.D., president of Merck Research Laboratories, emphasized this point, stating, "Enlicitide is a novel macrocyclic peptide that has the potential to deliver antibody-like efficacy and specificity for the validated PCSK9 mechanism in the form of a daily oral pill."

Merck's progress puts it ahead of competitor AstraZeneca in the oral PCSK9 inhibitor race. AstraZeneca's candidate, AZD0780, showed promising results in a phase 2 dyslipidemia study in March, halving cholesterol levels. However, Merck's phase 3 results position it closer to potential regulatory approval.

The news has been well-received by the market, with Merck's stock rising 2% in premarket trading following the announcement. Citi analysts described the data as "encouraging," projecting a potential approval for enlicitide in 2027 and noting its potential to be "a key player in the hyperlipidemia space."