Merck, known as MSD outside the US and Canada, has announced positive topline results from two Phase 3 trials evaluating enlicitide decanoate, an investigational oral PCSK9 inhibitor, for treating hyperlipidemia.
The CORALreef HeFH and CORALreef AddOn trials showed statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) compared to placebo and other oral non-statin therapies.
The two Phase 3 clinical trials met their primary and key secondary endpoints, showing greater reductions in LDL-C for enlicitide.
In the study, no clinically meaningful differences in adverse events (AE) and serious adverse events (SAE) were observed between the treatment and control groups in either trial.
Enlicitide is a potential first oral PCSK9 inhibitor, designed to lower LDL-C through the same biological mechanism as injectable monoclonal antibody PCSK9 inhibitors in a daily pill form.
The novel oral macrocyclic peptide binds to PCSK9, inhibiting its interaction with LDL receptors, increasing the number of LDL receptors available to remove LDL cholesterol.
Merck Research Laboratories president Dean Li said: “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 US.
“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. We are working with urgency to make this oral therapy available to patients worldwide.”
The CORALreef clinical development programme, which includes three Phase 3 trials, will present its results at a forthcoming scientific congress.
The programme aims to enrol around 17,000 patients across several trials, including ongoing studies, CORALreef Lipids and CORALreef Outcomes.
CORALreef HeFH is a randomised, double-blind, placebo-controlled, multicentre a Phase 3 study that evaluated the safety and efficacy of enlicitide.
The Phase 3 study enrolled heterozygous familial hypercholesterolemia (HeFH) at risk for atherosclerotic cardiovascular disease (ASCVD) and treated with statins.
The CORALreef AddOn trial assessed the efficacy of enlicitide against ezetimibe, bempedoic acid, and their combination in adults with hyperlipidemia at ASCVD risk.
CORALreef HeFH study principal investigator Christie Ballantyne said: “Atherosclerotic cardiovascular disease accounts for 85% of cardiovascular deaths.
“Despite available treatment options, cardiovascular-related deaths remain the leading cause of death worldwide and continue to rise.
“LDL-C is a major modifiable risk driver for atherosclerosis and prioritisation of LDL-C management should be a cornerstone of cardiovascular risk prevention. Early intervention and intensification of lipid treatment would allow more patients to achieve LDL-C goals.”
