Lilly Announces Positive Phase 2 Results for Muvalaplin, a First-in-Class Oral Therapy Significantly Reducing Lipoprotein(a) Levels
Eli Lilly
Global Pharmaceutical R&D and Production Company
· Muvalaplin, a once-daily oral medication that disrupts lipoprotein(a) formation through a novel mechanism, achieved positive results in a 12-week Phase 2 clinical study.
· Detailed data have been published in the Journal of the American Medical Association (JAMA) and simultaneously presented at the 2024 American Heart Association (AHA) Scientific Sessions.
Eli Lilly Announces Positive Results from Phase 2 Clinical Study of Muvalaplin. Muvalaplin is an investigational once-daily oral medication for reducing lipoprotein(a) [Lp(a)]. Lp(a) is a hereditary risk factor associated with cardiovascular disease. The study demonstrated that muvalaplin significantly reduced Lp(a) levels in adults, achieving the primary endpoint [i.e., the percentage change in Lp(a) from baseline to week 12].
At the primary endpoint of 12 weeks, muvalaplin (10mg, 60mg, and 240mg) significantly reduced Lp(a) levels compared to placebo. Using the full-length Lp(a) molecule assay, the placebo-adjusted reduction in Lp(a) was up to 85.8%, while using the apo(a) assay, the reduction was up to 70.0%. Specifically, with the full-length Lp(a) molecule assay, reductions were 47.6% (10mg), 81.7% (60mg), and 85.8% (240mg); with the apo(a) assay, reductions were 40.4% (10mg), 70.0% (60mg), and 68.9% (240mg).
Stephen J. Nicholls, PhD, Director of the Victoria Heart Hospital and Institute, and Professor of Cardiology at Monash University, Australia, stated:
Elevated Lp(a) levels have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting more than a billion adults worldwide. Current cholesterol-lowering therapies are not yet approved for reducing Lp(a), highlighting an unmet need for patients with cardiovascular disease. These data represent an important scientific advancement, with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes through a once-daily medication.
Eli Lilly is evaluating muvalaplin, a potent multivalent small molecule drug that reduces the formation of Lp(a) by interfering with the binding of apolipoprotein(a) [apo(a)] to apolipoprotein B (ApoB). In the United States, approximately 20% (around 63 million) of the population have elevated levels of Lp(a).1,2Elevated Lp(a) levels can double or even triple the risk of heart attack and are associated with other cardiovascular issues.3
Ruth Gimeno, Ph.D., Vice President of Eli Lilly and Company's Global Diabetes, Obesity, and Metabolic Disorders Research and Clinical Development, stated:
Although Lp(a) injectable formulations, including Eli Lilly's lepodisiran project, are currently in Phase 3 clinical trials, these study results represent the first positive Phase 2 clinical data for an Lp(a) oral formulation. We are pleased to see these encouraging results and look forward to further exploring the potential of muvalaplin.
All three studied doses of Muvalaplin (10mg, 60mg, and 240mg) met the secondary endpoints. All three doses demonstrated statistical significance in achieving the Lp(a) threshold levels, while the 60mg and 240mg doses also showed statistically significant improvements in ApoB reduction. These data further indicate:
Using the Lp(a) full molecule assay, the proportion of participants achieving Lp(a) levels below 125 nmol/L at week 12 was 64.2% in the 10 mg group, 95.9% in the 60 mg group, and 96.7% in the 240 mg group, compared to only 6.0% in the placebo group.
Using the apo(a) assay, the proportions of participants achieving Lp(a) levels below 125 nmol/L were: 38.9% in the 10mg group, 81.9% in the 60mg group, and 77.4% in the 240mg group, compared to only 3.6% in the placebo group.
Using the apo(a) assay, the proportions of participants achieving Lp(a) levels below 125 nmol/L were: 38.9% in the 10mg group, 81.9% in the 60mg group, and 77.4% in the 240mg group, compared to only 3.6% in the placebo group.
ApoB levels were reduced at all doses, with placebo-adjusted reductions of 8.9% in the 10mg group, 13.1% in the 60mg group, and 16.1% in the 240mg group.
In terms of the incidence of adverse events, the muvalaplin group and the placebo group were similar. The incidence of adverse events during treatment was as follows: 14.9% in the placebo group, 5.9% in the 10mg group, 14.3% in the 60mg group, and 14.7% in the 240mg group. The incidence of discontinuation due to adverse events ranged from 0% to 8.8% across the treatment groups, with these events being singular occurrences distributed across various system organ classes. No deaths were reported in the study.
Lilly
About Eli Lilly and Company
Eli Lilly and Company is a pharmaceutical company dedicated to improving human health through scientific innovation and benefiting patients worldwide. As a leader in the healthcare industry, Eli Lilly and Company has nearly 150 years of history. Today, our medicines have helped tens of millions of people around the world. Harnessing the power of biotechnology, chemistry, and genomic medicine, our scientists are actively advancing new medical breakthroughs to address severe global health challenges. We are redefining therapies for diabetes and obesity, reducing the long-term impact of obesity on the body; supporting prevention and treatment efforts for Alzheimer's disease; providing solutions for a range of immune-mediated diseases that threaten human health; and transforming difficult-to-treat cancers into manageable conditions. Every step Eli Lilly and Company takes toward a healthier world is driven by our belief in "making life better for millions of patients." This includes innovative clinical trials aimed at addressing multiple global challenges while ensuring the accessibility and affordability of medicines. For more information about Eli Lilly and Company, please visit: www.lilly.com.cn.
References
PP-MG-CN-3766