Muvalaplin Reduced Lipoprotein(a) by up to 85% in High-Risk Adults

INDIANAPOLIS, Nov. 18, 2024 – Eli Lilly and Company has announced promising outcomes from their Phase 2 trial of muvalaplin, an investigational drug taken orally once a day. Muvalaplin works as a selective inhibitor of lipoprotein(a) [Lp(a)], a genetically inherited factor that increases the risk of heart disease. The trial revealed that muvalaplin significantly lowered elevated Lp(a) levels in adults, successfully achieving its primary goal of measuring the percent change in Lp(a) from the beginning of the study to the 12-week mark.

The trial's primary endpoint at week 12 displayed significant reductions in Lp(a) levels for muvalaplin doses of 10 mg, 60 mg, and 240 mg compared to a placebo. The reductions, adjusted for the placebo, reached up to 85.8% using an intact Lp(a) assay and up to 70.0% using an apo(a) assay. Specifically, the reductions were 47.6% (10 mg), 81.7% (60 mg), and 85.8% (240 mg) with the intact Lp(a) assay, and 40.4% (10 mg), 70.0% (60 mg), and 68.9% (240 mg) with the apo(a) assay.

Stephen J. Nicholls, MBBS, Ph.D., the director of the Victorian Heart Hospital and Institute and a cardiology professor at Monash University in Australia, emphasized the importance of these findings. He noted that high Lp(a) levels are a significant risk factor for atherosclerotic cardiovascular disease, affecting over a billion adults worldwide. Current cholesterol-lowering treatments do not target Lp(a) levels, leaving a gap in treatment options for those with cardiovascular disease. The data from this study represent a significant scientific advancement, offering the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a daily pill.

Eli Lilly is studying muvalaplin, a strong, multivalent small molecule designed to inhibit the formation of Lp(a) by blocking the initial interaction between apolipoprotein(a) [apo(a)] and apolipoproteinB (apoB). In the United States, approximately 20% of the population, or around 63 million people, have high Lp(a) levels. Elevated Lp(a) levels can significantly increase the risk of heart attacks and other cardiovascular problems.

Ruth Gimeno, Ph.D., group vice president of Diabetes and Metabolic Research at Lilly Research Laboratories, expressed satisfaction with the Phase 2 data. She highlighted that while injectable therapies for Lp(a) are currently in Phase 3 development, including Lilly's own lepodisiran program, this is the first set of positive Phase 2 results for an oral method. Lilly is eager to explore the next steps for muvalaplin.

Additionally, muvalaplin met secondary endpoints for all three doses tested (10 mg, 60 mg, and 240 mg). The doses achieved statistical significance for Lp(a) thresholds, and the 60 mg and 240 mg doses also reached statistical significance for apoB reductions. The data also indicated:

- Adverse events were comparable between the muvalaplin and placebo groups. Treatment-emergent adverse events related to the study drug were observed 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 the discontinuation of the study drug ranged from 0 to 8.8% across treatment groups and were isolated events across various system organ classes. No deaths were reported during the study.

About Eli Lilly:
Eli Lilly and Company has been dedicated to transforming science into healing for nearly 150 years. Their innovative medicines have improved the lives of millions worldwide. Harnessing biotechnology, chemistry, and genetic medicine, Lilly's scientists are making strides in addressing some of the globe's most significant health challenges, including diabetes, obesity, Alzheimer's disease, immune system disorders, and formidable cancers. Their commitment includes conducting diverse and inclusive clinical trials and ensuring that their medicines are both accessible and affordable.