Lilly's Lepodisiran Shows Promise in Lowering Lipoprotein(a), Challenging Competitors

Eli Lilly has reported promising phase 2 results for its siRNA candidate lepodisiran, demonstrating sustained reductions in lipoprotein(a) (Lp(a)) levels for nearly 1.5 years. The data, presented at the American College of Cardiology 2025 Scientific Sessions, positions Lilly's drug as a potential frontrunner in the race to address elevated Lp(a), a significant risk factor for cardiovascular disease affecting up to 2 billion people globally.

Impressive Efficacy and Durability

The phase 2 trial, involving 320 participants, tested three doses of lepodisiran against placebo. The highest dose (400mg) achieved an average Lp(a) reduction of 93.9% over the 60 to 180-day period post-treatment. Notably, the effect persisted long after the final dose, with Lp(a) levels remaining 91% below baseline at Day 360 and 74.2% below baseline at Day 540.

Lilly's Chief Scientific Officer, Daniel Skovronsky, M.D., Ph.D., highlighted two potential advantages of lepodisiran: "First is the depth of clearance of Lp(a)... The second ... could be frequency of administration or durability of action, those two being closely linked."

Competitive Landscape

Lilly's results come amidst fierce competition in the Lp(a)-lowering space. Amgen's olpasiran and Novartis's pelacarsen are currently leading the pack with ongoing phase 3 trials expected to conclude next year. Amgen previously reported a 95% placebo-adjusted Lp(a) reduction in its phase 2 trial, with levels remaining 40% to 50% lower than placebo nearly a year after treatment cessation.

While Lilly's phase 3 trial for lepodisiran isn't scheduled to complete until 2029, the recent data suggests potential advantages in terms of dosing frequency and durability. The phase 2 results indicate that lepodisiran could maintain significant Lp(a) suppression with bi-annual dosing, compared to monthly administration for pelacarsen and quarterly for olpasiran in their respective phase 3 trials.

Future Implications

As the race to develop effective Lp(a)-lowering therapies intensifies, the pharmaceutical industry eagerly awaits the outcomes of ongoing phase 3 trials. The potential market for these treatments is substantial, given the large population affected by elevated Lp(a) and the lack of established therapies targeting this specific risk factor.

While Lilly may be behind its competitors in terms of development timeline, the impressive durability and efficacy demonstrated by lepodisiran could potentially give it a competitive edge. Additionally, the company is exploring oral drugs for reducing Lp(a), further diversifying its approach to addressing this unmet medical need.