A phase 2 trial known as ALPACA has shown that lepodisiran, a long-acting small interfering RNA therapy, can significantly reduce lipoprotein(a) [Lp(a)] levels in patients with elevated Lp(a]. The results were presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions.
The trial found that patients receiving lepodisiran achieved reductions of 40.8%, 75.2%, and 93.9% for the 16 mg, 96 mg, and pooled 400 mg dose groups, respectively. These effects were observed to last up to 18 months.
Eli Lilly announced plans to move forward with the phase 3 ACCLAIM-Lp(a) trial after demonstrating the therapy’s potential. Dr. Steve Nissen, chief academic officer of the Heart Vascular & Thoracic Institute at the Cleveland Clinic, noted that nearly a quarter of the world’s population has elevated Lp(a], increasing cardiovascular risk and highlighting the need for effective treatments.
The trial involved 320 patients across 66 sites on five continents, with no serious adverse events linked to lepodisiran. However, treatment-emergent adverse events were reported in some patients receiving higher doses of the therapy.
These findings suggest that siRNA approaches like lepodisiran could offer durable benefits with long-term dosing for reducing Lp(a] levels and related cardiovascular risk.
Source: https://www.hcplive.com/view/lepodisiran-alpaca-and-lp-a-with-steve-nissen-md