Merck’s enlicitide decanoate significantly lowered low-density lipoprotein cholesterol in two Phase III trials, unlocking what BMO Capital Markets called a “multi-billion dollar opportunity” for the pharma.
Merck’s investigational PCSK9 inhibitor enlicitide decanoate significantly lowered low-density lipoprotein cholesterol in patients with abnormally high lipid blood levels in two Phase III readouts, the company reported Monday.
In a note to investors Monday, BMO Capital Markets said the readout advances the pharma’s cardiovascular portfolio. These latest findings “could potentially provide a multi-billion dollar opportunity expanding the PCSK9 market beyond current injectable therapies,” they wrote.
The topline results come from the placebo-controlled CORALreef HeFH study, which enrolled adults with heterozygous familial hypercholesterolemia (HeFH), and from the CORALreef AddOn trial, which focused on patients with hypercholesterolemia and which used ezetimibe and bempedoic acid—two oral non-statin agents—as comparators. In both studies, participants had a history of or were at risk of atherosclerotic cardiovascular disease, and were also being managed with statins.
The pharma did not provide specific data from either study, announcing only that treatment with enlicitide decanoate resulted in “statistically significant and clinically meaningful reductions” in low-density lipoprotein cholesterol versus the respective controls. Enlicitide decanoate likewise met all of its key secondary endpoints in both studies.
In their Monday note, BMO agreed that the topline readouts “positively advance the company’s oral PCSK9 therapy,” adding that Merck’s safety disclosures have “largely de-risked” enlicitide decanoate “at this time.” Adverse events (AE) and serious AEs were balanced among treatment arms in either trial, according to Merck.
“Details in the topline release were limited,” BMO wrote. “It was noted that there were no meaningful differences in incidence of AEs or serious AEs in both trials, largely aligning with prior Ph2 results and giving us further confidence in the drug’s efficacy profile.”
Enlicitide decanoate is an orally available inhibitor of the PCSK9 protein, which under healthy conditions helps regulates the uptake of cholesterol into cells. With its mechanism of action, enlicitide decanoate allows cells to remove more low-density lipoprotein—aka. “bad cholesterol” from the blood.
Aside from CORALreef HeFH and CORALreef AddOn, Merck is testing enlicitide decanoate in two other late-stage trials: CORALreef Lipids and CORALreef Outcomes. The Lipids study is expected to wrap up later this year, as per the BMO note, while the Outcomes trial has a primary completion date of November 2029.
Merck did not detail its regulatory plans for the drug in Monday’s release but noted that if approved, enlicitide decanoate would become the first oral PCSK9 inhibitor on the market.
