Eli Lilly and Company has announced positive Phase 2 results for Muvalaplin, an investigational small molecule drug targeting lipoprotein(a) (Lp(a)), a genetic risk factor for heart disease. The trial demonstrated that Muvalaplin significantly reduced Lp(a) levels in adults at high risk for cardiovascular events, meeting both primary and secondary endpoints at 12 weeks.
Targeting Lipoprotein(a) for Cardiovascular Risk Reduction
Lp(a) affects approximately 63 million people in the U.S. and over one billion adults globally. Elevated levels of Lp(a) contribute to the formation of plaques in blood vessel walls, impeding blood flow to vital organs and increasing the risk of heart attack, stroke, and other cardiovascular diseases. Muvalaplin functions by inhibiting the interaction between apolipoprotein(a) and apolipoprotein B, thereby preventing Lp(a) formation.
Phase 2 Trial Results
The Phase 2 study involved participants receiving Muvalaplin in three different dosages (10mg, 60mg, and 240mg) compared to a placebo. Results indicated that all dosages of Muvalaplin led to a reduction in Lp(a) levels relative to the placebo group. The highest dosage (240mg) achieved up to an 85.8% reduction in Lp(a) levels, as measured by an Lp(a) assay, and up to a 70% reduction, as measured by an apolipoprotein(a) assay.
Expert Commentary
"High levels of Lp(a) have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting over one billion adults globally," said Stephen J. Nicholls, Director of the Victorian Heart Hospital and Institute, and Professor of Cardiology at Monash University, Australia. "Current cholesterol-lowering therapies are not approved to lower Lp(a) levels, highlighting an unmet need for people living with cardiovascular disease. These data represent a needed scientific advancement with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a once-daily pill."
Implications and Future Directions
Ruth Gimeno, Group Vice President of Diabetes and Metabolic Research at Lilly Research Laboratories, noted the significance of these findings: "While injectable approaches for Lp(a) are currently in Phase 3 development, including Lilly's own lepodisiran program, these are the first positive Phase 2 data for an oral approach. We are very pleased to see these promising results and look forward to further exploring next steps for Muvalaplin."
The development of Muvalaplin represents a potentially significant advancement in cardiovascular disease treatment, offering a novel oral therapy to address elevated Lp(a) levels, a critical unmet need in managing cardiovascular risk.
