Enlicitide Achieves Significant LDL-C Reductions in ASCVD Patients

A recent clinical trial has shown that the oral medication enlicitide significantly reduces low-density lipoprotein cholesterol (LDL-C) levels in patients at risk for atherosclerotic cardiovascular disease (ASCVD). The findings from the phase 3 CORALreef Lipids trial have been published in The New England Journal of Medicine, highlighting the drug’s potential to transform treatment options for individuals with elevated cholesterol levels.

The study involved 2,904 participants aged 18 and older, all of whom either had a history of a major ASCVD event or were at high risk for such events. Participants had LDL-C levels of at least 55 mg/dL or 70 mg/dL, and they had been on stable lipid-lowering therapy for at least 30 days before the trial, which included moderate- or high-intensity statins. Participants were randomly assigned to receive either 20 mg of enlicitide (n = 1,935) or a placebo (n = 969).

At the 24-week mark, those receiving enlicitide experienced an average reduction in LDL-C levels of approximately 57.1% compared to a mere 3.0% increase in the placebo group. This substantial difference met the study’s primary endpoint, with an adjusted between-group difference of 55.8%, demonstrating the efficacy of enlicitide as a treatment option (P < .001).

Positive Outcomes Beyond LDL-C Reduction

The trial also examined key secondary endpoints, including changes in non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)]. Results showed that non–HDL-C decreased by around 53.4%, ApoB by 50.3%, and Lp(a) by 28.2% by the end of the study period, all with high statistical significance (P < .001). An important finding was that over 70% of participants receiving enlicitide achieved LDL-C levels below 70 mg/dL with more than a 50% reduction from baseline. In contrast, only 1.5% of the placebo group reached these levels. Furthermore, 67.5% of enlicitide patients achieved LDL-C levels below 55 mg/dL, again demonstrating a stark contrast to just 1.2% among placebo recipients.

Safety assessments indicated that the incidence of adverse events was comparable between the enlicitide and placebo groups, suggesting that the treatment is well-tolerated.

Implications for Cardiovascular Treatment

The results indicate that enlicitide could significantly advance the treatment landscape for patients with high cholesterol and cardiovascular risk. As a PCSK9 inhibitor, it offers a new avenue for lipid-lowering therapy when used alongside statins. Its oral formulation presents a more convenient option for patients, potentially leading to improved adherence compared to existing injectable alternatives.

Dr. Ann Marie Navar, an associate professor of internal medicine and a member of the Division of Cardiology at UT Southwestern Medical School, emphasized the drug’s effectiveness: “With a nearly 60% reduction in LDL-C when given on top of background therapy, this offers a great option for patients who are above goal and need additional non-statin therapy.”

Dr. Joseph Saseen, a professor and associate dean for clinical affairs at the University of Colorado Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences, expressed optimism regarding the broader accessibility of enlicitide: “There is the hope that this can be more deployable to a broader patient population, as far as an option that can fit the scheme of how patients usually take their maintenance medications.”

The potential impact of enlicitide has garnered significant attention, leading to the receipt of a national priority voucher from the FDA. This voucher aims to expedite the review and approval processes for the drug, addressing the pressing need for effective therapies to combat rising cardiovascular risks.