Merck & Co. has lifted the lid on the third successful phase 3 trial of its PCSK9 inhibitor, showing the edge the cardiovascular disease prospect has over other oral non-statin therapies.
Last year, Merck said the study, dubbed Coralreef AddOn, met its primary and key secondary endpoints, but the company kept the data back for a medical meeting. The Big Pharma arrived at the American College of Cardiology’s annual get-together clutching the data, which show its oral macrocyclic peptide enlicitide comfortably beat the control treatments across multiple measures of cardiovascular health.
Investigators randomized 301 statin-treated adults with atherosclerotic cardiovascular disease to receive enlicitide or one of three control regimens. Patients in the control arms took bempedoic acid, ezetimibe or both approved drugs in combination.
On Day 56, LDL cholesterol (LDL-C) had fallen by an average of 64.6% in the enlicitide cohort. Patients on the combination of bempedoic acid and ezetimibe had the next biggest decline in LDL-C, but the drop lagged well behind the study drug at 36.5%.
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Enlicitide drove deeper declines than the control treatments in apolipoprotein B (ApoB) and non-HDL cholesterol (non-HDL-C), hitting key secondary endpoints. Specifically, enlicitide reduced ApoB by 54.6%, compared to the next largest reduction of 27.7% from bempedoic acid with ezetimibe combined. Meanwhile, the study drug was linked to a 58.0% drop in non-HDL-C compared to the next-best reduction of 31.8% for bempedoic acid and ezetimibe.
Merck’s abstract lacked detailed safety and tolerability data. The company said the drug candidate was well-tolerated, a finding that is in line with the results of its other studies. Enlicitide had a placebo-like safety profile in Coralreef Lipids, another of Merck’s three successful phase 3 trials.
After reviewing the Coralreef Lipids results last year, Guggenheim Securities analysts said in a note to investors that they see a path for enlicitide sales to exceed the $2.8 billion consensus revenue estimate for 2033. The analysts and their peers at BMO Capital Markets both noted the need for patients to take enlicitide on an empty stomach as a potential issue, although adherence was high in the phase 3 trials.
“The consistency of the results from CORALreef AddOn, together with the data from CORALreef Lipids and CORALreef HeFH, further establish the efficacy and safety profile of enlicitide as a promising potential treatment solution for patients in need of further LDL-C reduction,” Joerg Koglin, M.D., senior vice president, head of general and specialty medicine, global clinical development, Merck Research Laboratories.
Merck Chief Financial Officer Caroline Litchfield said at a TD Cowen event on March 3 that the company intended to file for FDA approval of enlicitide imminently. Typically, the timing would position Merck to launch enlicitide early in 2027. However, Merck has received a Commissioner’s National Priority Voucher for enlicitide, leading Litchfield to express hopes that the product could come to market sooner.
