Lilly's Oral Muvalaplin Significantly Reduces Lipoprotein(a) Levels in Phase II Trial

• Eli Lilly's muvalaplin, an oral drug, significantly reduced lipoprotein(a) (Lp(a)) levels in a Phase II study, meeting the primary endpoint.
• The study showed dose-dependent reductions in Lp(a) levels, with the 60 mg and 240 mg doses achieving reductions of 81.7% and 85.8%, respectively.
• Muvalaplin's novel mechanism disrupts the interaction between apolipoprotein(a) and apolipoprotein(b), preventing Lp(a) formation.
• Current cholesterol-lowering medicines are not approved to lower Lp(a) levels, highlighting muvalaplin's potential to address an unmet need.

Eli Lilly has announced positive results from its Phase II trial of muvalaplin, an investigational oral, once-daily drug designed to lower lipoprotein(a) (Lp(a)) levels. The study demonstrated a significant reduction in elevated Lp(a) levels in adults at high risk of cardiovascular events, achieving the primary endpoint of percent change in Lp(a) from baseline to week 12.

Significant Lp(a) Reduction Across Multiple Doses

The Phase II trial revealed notable dose-dependent reductions in Lp(a) levels. Using an intact Lp(a) assay, the 10 mg dose of muvalaplin resulted in a 47.6% reduction, while the 60 mg and 240 mg doses led to reductions of 81.7% and 85.8%, respectively. Measurements using an apo(a) assay also showed substantial reductions: 40.4% (10 mg), 70.0% (60 mg), and 68.9% (240 mg). The drug also met secondary endpoints for all three doses.

Addressing Unmet Needs in Cardiovascular Disease

Elevated Lp(a) levels are a significant risk factor for coronary disease, contributing to arterial blockage and increasing the risk of heart disease and stroke. Currently, available cholesterol-lowering medications are not approved for lowering Lp(a) levels, creating a substantial unmet need in cardiovascular care. Muvalaplin, with its novel mechanism of action, presents a potential solution by disrupting the interaction between apolipoprotein(a) and apolipoprotein(b), thereby preventing the formation of Lp(a).

Novel Mechanism of Action

Muvalaplin's unique approach targets the root cause of elevated Lp(a) by interfering with the assembly of the lipoprotein. Apolipoprotein(a) is a key component of Lp(a), and by preventing its interaction with apolipoprotein(b), muvalaplin effectively reduces Lp(a) levels. This mechanism differs from existing therapies and offers a targeted strategy for managing cardiovascular risk associated with elevated Lp(a).

Competition in Lp(a) Lowering Therapies

While muvalaplin is an oral therapy, other companies are developing injectable treatments for lowering Lp(a). Lilly is also advancing lepodisiran, an RNA-based candidate, in Phase III studies. Novartis, in partnership with Ionis Pharmaceuticals, is developing pelacarsen, and Amgen is working on olpasiran, both of which are injectable RNA-based therapies in Phase III trials. Phase II data for Amgen’s olpasiran demonstrated Lp(a) reductions of over 95% in patients with established atherosclerotic cardiovascular disease.