Merck's MK-0616 Aims to Cut LDL-C in Hypercholesterolemia Phase 3 Study

By: Marc Steven Sabatine, MD, MPH - Lewis Dexter, MD Distinguished Chair in Cardiovascular Medicine
Professor, Harvard Medical School

Date: 9/14/2023

In the realm of cardiovascular research, Marc S. Sabatine, MD, MPH, is leading groundbreaking studies to evaluate the potential of MK0616, an investigational once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Developed by Merck (NYSE: MRK), also known as MSD outside the United States and Canada, this compound holds immense promise for the management of hypercholesterolemia.

Merck has announced three pivotal studies to explore MK0616's potential. One key trial aims to assess MK0616's effect on LDL cholesterol levels in a phase three trial. Building on phase two B trial data, it demonstrated significant reductions in LDL cholesterol levels, ranging from 40% to 60%, across various doses. This phase three trial plans to confirm these findings in a larger population, with around 2,700 to 2,800 patients and a year of follow-up data—a duration in line with regulatory standards for drug approval based on LDL cholesterol reduction. Another trial focuses on patients with familial hypercholesterolemia, a challenging condition due to high LDL cholesterol levels. This subset, affecting approximately one in 250 adults, will undergo a dedicated trial to assess MK0616's efficacy.

The largest trial, the cardiovascular outcomes trial, features over 14,000 patients and aims to establish the clinical efficacy of LDL cholesterol lowering with MK0616. It spans an average follow-up of about five years, reflecting the drug's potential significance in managing cardiovascular risk.

MK0616's appeal lies in its ability to target PCSK9, a well-validated cardiovascular target. This approach builds upon robust epidemiological and genetic data and the success of monoclonal antibodies in targeting PCSK9. What sets MK0616 apart is its potential as an oral option—a convenient daily pill compared to the injectable alternatives currently available.

Merck has reported promising results from a Phase 2b clinical trial, evaluating MK0616's efficacy in reducing LDL cholesterol levels in adults with hypercholesterolemia. At week 8, all doses of MK0616 significantly reduced LDL cholesterol compared to placebo, with reductions ranging from 41.2% to 60.9%. Importantly, MK0616 was well-tolerated across all four doses studied, raising hopes for a more accessible, convenient oral treatment option for hypercholesterolemia.

Hypercholesterolemia management remains a persistent challenge, with many patients struggling to achieve recommended cholesterol levels. The promising data showing MK0616's substantial LDL cholesterol reduction of up to 60.9% suggest that it merits further investigation as a daily oral medicine.

Merck's commitment to advancing this program into Phase 3 development in the latter half of 2023 reflects their dedication to improving patient outcomes. The research led by Marc S. Sabatine and the promising results from Merck's Phase 2b trial paint a hopeful picture for the future of hypercholesterolemia management. MK0616, with its potential to provide convenient, effective LDL cholesterol reduction, has the potential to transform the landscape of cardiovascular care, offering a promising alternative to existing treatments and underscoring Merck's commitment to cardiovascular health.