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Encouraging data for lepodisiran as Lp(a) lowering therapy

Presented by
Dr Steven Nissen, Cleveland Clinic, OH, USA
AHA 2023
Phase 1
A substantial reduction in lipoprotein(a) was achieved with a single subcutaneous injection of lepodisiran, an siRNA-targeting mRNA for the LPA gene. Together with the favourable safety profile of this agent, the results support further exploration of lepodisiran.

The current phase 1 trial (NCT04914546) evaluated the safety and efficacy of lepodisiran in 48 participants with Lp(a) concentrations ≥75 nmol/L who did not have known cardiovascular disease at enrolment. “Participants were randomised to 1 of 6 single-dose levels of lepodisiran, ranging from 4 mg to 608 mg, or to a placebo, all subcutaneously administered,” explained Dr Steven Nissen (Cleveland Clinic, OH, USA) [1]. The primary outcome measures were safety and Lp(a) serum concentrations through 48 weeks.

At 48 weeks, the mean reduction in Lp(a) was 94% in the highest dose group, showing an excellent duration of the effect that lepodisiran has on Lp(a) levels. The rate of adverse events (AEs) was overall low, and no dose-related trend could be observed in the occurrence of AEs. Headache, COVID-19, rhinorrhoea, and ECG patch erythema were the most common AEs. Injection-site reactions were reported as well, but not more frequently in the active arms than in the placebo arm.

Thus, lepodisiran delivered promising results as an Lp(a)-lowering agent in the current phase 1 study, supporting further development of the drug.

  1. Nissen SE, et al. Lepodisiran: an extended-duration siRNA targeting lipoprotein(a). LB06, AHA Scientific Sessions 2023, 10–12 November, Philadelphia, PA, USA.


Medical writing support was provided by Robert van den Heuvel.

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