Photo Credit: Artemis Diana
A single subcutaneous injection of lepodisiran resulted in substantial lipoprotein(a) reduction in the phase 1 trial.
A substantial reduction in lipoprotein(a) was achieved with a single subcutaneous injection of lepodisiran, a siRNA-targeting mRNA for the LPA gene. Together with the favorable 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 of at least 75 nmol/L who did not have known cardiovascular disease at enrolment. “Participants were randomized to 1 of 6 single-dose levels of lepodisiran, ranging from 4 mg to 608 mg, or to a placebo, all subcutaneously administered,” explained Steven Nissen, MD (Cleveland Clinic).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 less 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 drug development.
Medical writing support was provided by Robert van den Heuvel.
Copyright ©2023 Medicom Medical Publishers
