Merck & Co.’s ambition to get the first oral PCSK9 inhibitor to market came one step closer this morning as the pharma unveiled a pair of phase 3 wins for enlicitide decanoate in patients with high cholesterol.
Merck evaluated the candidate in two studies, including the CORALreef HeFH trial of patients with heterozygous familial hypercholesterolemia who had suffered from, or had a risk of, atherosclerotic cardiovascular disease and were being treated with a statin. The trial hit its primary endpoint of showing a clinically meaningful reduction in baseline levels of low-density lipoprotein cholesterol (LDL-C) at Week 24 compared to placebo, Merck explained in a June 9 release.
When it came to the CORALreef AddOn study of hypercholesterolemia patients, the study also hit its key endpoint of showing a reduction in LDL-C at Week 8 compared to the approved non-statin cholesterol medicines ezetimibe or bempedoic acid.
Merck didn’t divulge any detailed data behind the wins, only noting that there were “no clinically meaningful differences in incidences of adverse events” in either trial. The two studies form part of the company’s wider CORALreef development program, which spans 17,000 patients in total and also includes the ongoing CORALreef Lipids and CORALreef Outcomes phase 3 trials.
The hypercholesterolemia market is currently dominated by injectable PCSK9 inhibitors in the form of Amgen’s Repatha and Sanofi-Regeneron’s Praluent. Meanwhile, Novartis’ Leqvio uses small-interfering RNA technology to decrease PCSK9 production in the liver.
Enlicitide uses the same mechanism as approved monoclonal antibody injectable PCSK9 inhibitors but would give patients an oral alternative, potentially making it more attractive in terms of administration.
Today’s double win keeps Merck ahead of its rival AstraZeneca when it comes to getting the first oral PCSK9 inhibitor to regulators. The British-based pharma’s option is AZD0780, which was shown to halve cholesterol in a phase 2 dyslipidemia study in March.
“We are thrilled to bring forward the first phase 3 results from our clinical development program evaluating enlicitide, which, if approved, would be the first marketed oral PCSK9 inhibitor in the U.S.,” Dean Li, M.D., Ph.D., president of Merck Research Laboratories, said in the release.
“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,” Li added. “We are working with urgency to make this oral therapy available to patients worldwide.”
Citi analysts described this morning’s data as “encouraging” ahead of an anticipated approval in 2027.
“We believe enlicitide could be a key player in the hyperlipidemia space, where an oral administration along with a positive efficacy and safety profile could be differentiating,” the analysts wrote in a June 9 note.
https://www.fiercebiotech.com/biotech/mercks-leader-oral-pcsk9-inhibitor-race-reduces-cholesterol-pair-phase-3-trials
