Eli Lilly and Company (NYSE: LLY) has revealed encouraging Phase 2 results for muvalaplin, an investigational once-daily oral inhibitor targeting lipoprotein(a) [Lp(a)], a hereditary risk factor for cardiovascular disease. The trial demonstrated that muvalaplin significantly lowered elevated Lp(a) levels, achieving its primary endpoint: percent change in Lp(a) from baseline to week 12.
Key Findings
At 12 weeks, muvalaplin delivered substantial placebo-adjusted reductions in Lp(a) levels across all doses tested (10 mg, 60 mg, and 240 mg). Results showed reductions of up to:
- 85.8% using an intact Lp(a) assay
- 70.0% using an apo(a) assay
Specifically, the reductions with the intact Lp(a) assay were:
- 47.6% (10 mg)
- 81.7% (60 mg)
- 85.8% (240 mg)
For the apo(a) assay, reductions were:
- 40.4% (10 mg)
- 70.0% (60 mg)
- 68.9% (240 mg)
Expert Commentary
“Elevated Lp(a) significantly raises the risk of atherosclerotic cardiovascular disease and currently lacks approved treatments,” said Stephen J. Nicholls, MBBS, Ph.D., professor of cardiology at Monash University. “These findings offer a significant step forward, potentially reducing cardiovascular risks like heart attacks and strokes with a simple daily pill.”
Mechanism of Action and Context
Muvalaplin is a small molecule inhibitor that prevents Lp(a) formation by disrupting the interaction between apolipoprotein(a) [apo(a)] and apolipoprotein B (apoB). Elevated Lp(a) affects approximately 20% of the U.S. population—about 63 million people—and can double or triple the risk of heart attacks and other cardiovascular events.
Ruth Gimeno, Ph.D., group vice president of Diabetes and Metabolic Research at Lilly, highlighted the significance of this oral therapy: “These are the first positive Phase 2 results for an oral Lp(a) treatment. We’re thrilled with the progress and look forward to advancing muvalaplin further.”
Secondary Endpoints and Additional Data
Muvalaplin also met secondary endpoints, including Lp(a) thresholds and apoB reductions:
- Intact Lp(a) assay: Up to 96.7% of participants achieved Lp(a) levels <125 nmol/L (compared to 6.0% with placebo).
- Apo(a) assay: Up to 81.9% achieved <125 nmol/L (compared to 3.6% with placebo).
- ApoB reductions ranged from 8.9% to 16.1%, depending on the dose.
Safety and Tolerability
Adverse events were similar between muvalaplin and placebo groups:
- Treatment-emergent adverse events occurred in 14.9% of the placebo group and 5.9% to 14.7% across muvalaplin doses.
- Discontinuations due to adverse events varied from 0% to 8.8%, with no deaths reported.
With these promising Phase 2 results, muvalaplin marks a potential breakthrough in addressing the unmet need for effective Lp(a)-lowering therapies in cardiovascular care.
