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Highlights

  • Significant Reduction: Lepodisiran lowered Lp(a) levels by up to 93.9%, meeting the primary endpoint in Phase 2 trials.

  • Long-Lasting Effect: A 400 mg dose sustained a 91.0% reduction for a year and 74.2% reduction for 1.5 years.

  • No Serious Safety Concerns: While some treatment-related adverse events were reported, no serious side effects were linked to lepodisiran.

Eli Lilly and Company (NYSE:LLY) has announced positive Phase 2 results for lepodisiran, an investigational small interfering RNA (siRNA) therapy designed to lower lipoprotein(a) [Lp(a)] levels, a genetic risk factor for cardiovascular disease. The ALPACA study results confirm that lepodisiran successfully met its primary and secondary endpoints, demonstrating a significant and prolonged reduction in Lp(a) levels.

Lepodisiran’s Impact on Lp(a) Reduction

The study found that participants receiving a 400 mg dose of lepodisiran experienced a 93.9% reduction in Lp(a) levels between days 60 and 180 post-treatment. Those receiving lower doses also saw notable reductions, with the 16 mg dose decreasing Lp(a) by 40.8% and the 96 mg dose by 75.2% over the same period.

Additionally, a second 400 mg dose at day 180 sustained reductions throughout the study, with Lp(a) levels remaining 91.0% below baseline at one year and 74.2% below baseline at 1.5 years. These findings suggest lepodisiran could offer a long-lasting solution for patients with elevated Lp(a), who are at higher risk of heart disease.

Potential for Broader Cardiovascular Benefits

Lepodisiran also reduced apolipoprotein B (apoB) levels, a key cholesterol biomarker associated with heart disease. The 400 mg dose lowered apoB by 14.1% at day 60 and 13.7% at day 180, with sustained reductions through day 540 when an additional dose was administered.

Approximately 20% of Americans have high Lp(a) levels, which can double or even triple the risk of heart attack and are associated with conditions such as stroke and aortic valve stenosis. Current treatment options for Lp(a) reduction are limited, making lepodisiran a potential game-changer in cardiovascular medicine.

Safety and Next Steps

The study reported no serious adverse events linked to lepodisiran. However, mild to moderate treatment-emergent adverse events (TEAEs) occurred in 14% of patients receiving the highest dose. Importantly, no participants withdrew from the study due to TEAEs.

Encouraged by these promising results, Eli Lilly has launched the ACCLAIM-Lp(a) Phase 3 trial, which aims to assess whether lepodisiran can reduce cardiovascular events in patients with elevated Lp(a) levels. Enrollment for this pivotal study is currently underway, bringing the potential one step closer to clinical use.