Lilly's muvalaplin reduces lipoprotein(a) in high-risk adults

Eli Lilly and Company has announced successful results from a Phase 2 clinical trial of muvalaplin, an investigational oral treatment taken once daily that inhibits the formation of lipoprotein(a) or Lp(a). Elevated Lp(a) levels are a known genetic risk factor for heart disease. The study, whose findings have been published in the Journal of the American Medical Association (JAMA) and presented at the American Heart Association (AHA) Scientific Sessions 2024, showed that muvalaplin significantly reduced Lp(a) levels in adults over a 12-week period.

The trial’s primary endpoint was the percentage change in Lp(a) levels from baseline to week 12. Muvalaplin was tested at doses of 10 mg, 60 mg, and 240 mg, and each dose resulted in significant reductions in Lp(a) levels compared to a placebo. The reductions using an intact Lp(a) assay were 47.6% for the 10 mg dose, 81.7% for the 60 mg dose, and 85.8% for the 240 mg dose. When measured using an apo(a) assay, the reductions were 40.4%, 70.0%, and 68.9% respectively for the 10 mg, 60 mg, and 240 mg doses.

Stephen J. Nicholls, MBBS, Ph.D., director of the Victorian Heart Hospital and Institute, and professor of cardiology at Monash University in Australia, commented on the findings: “High levels of Lp(a) have been identified as a major risk factor for atherosclerotic cardiovascular disease, impacting over one billion adults worldwide. Current cholesterol-lowering therapies do not address Lp(a) levels, highlighting a significant unmet need for effective treatments. The data from this study represent a promising scientific advancement, with the potential to reduce cardiovascular risks such as heart attacks and strokes with a simple once-daily pill.”

Muvalaplin works by blocking the initial interaction between apolipoprotein(a) [apo(a)] and apolipoproteinB (apoB), thereby preventing the formation of Lp(a). In the United States, about 20% of the population, approximately 63 million people, have elevated Lp(a) levels, which can double or even triple the risk of heart attacks and other cardiovascular issues.

Ruth Gimeno, Ph.D., group vice president of Diabetes and Metabolic Research at Lilly Research Laboratories, remarked, "While injectable treatments for Lp(a) are currently in Phase 3 development, including Lilly’s own lepodisiran program, these Phase 2 results are the first positive data for an oral treatment approach. We are very excited by these results and are looking forward to further development of muvalaplin."

In addition to achieving its primary endpoint, muvalaplin also met secondary endpoints across all three tested doses. Statistical significance was observed for Lp(a) thresholds for all tested doses, and for apoB reductions at the 60 mg and 240 mg doses.

The safety profile of muvalaplin was similar to that of the placebo, with adverse events related to the study drug occurring in 14.9% of the placebo group, 5.9% of the 10 mg group, 14.3% of the 60 mg group, and 14.7% of the 240 mg group. The incidence of adverse events leading to discontinuation of the study drug ranged from 0 to 8.8% across treatment groups, with no deaths reported during the study.

Eli Lilly and Company has a long history of pioneering medical discoveries and developing treatments to improve global health. Their work spans a range of significant health challenges, including diabetes, obesity, Alzheimer’s disease, immune system disorders, and cancer. The company remains committed to advancing new treatments and ensuring their accessibility and affordability to people worldwide.