A Long-Duration Small Interfering RNA to Lower Lipoprotein(a)?

In a phase 2 manufacturer-funded trial, lepodisiran safely reduced Lp(a) levels in a dose-dependent manner.

Lipoprotein(a) [Lp(a)] is a lipid-related particle that is associated with atherosclerotic cardiovascular disease. Lepodisiran is a non–FDA-approved, extended-duration, small interfering RNA that was shown to lower Lp(a) levels in a phase 1 study (NEJM JW Cardiol Nov 13 2023 and JAMA 2023; 330:2075). Now, the manufacturers have performed a phase 2 study to further evaluate its safety and efficacy for Lp(a) lowering (NCT05565742).

Investigators randomized 320 participants aged ≥40 years with elevated Lp(a) levels (median, 253.9 nmol/L) to receive subcutaneous injections of lepodisiran at doses of 16 mg, 96 mg, or 400 mg at baseline and day 180; a dose of 400 mg at baseline and placebo at day 180; or placebo at both baseline and day 180.

Betwee…

Reviewing Author

Karol E. Watson, MD, PhD, FACC

Disclosures

Consultant/Advisory BoardBoehringer Ingelheim; Amgen; Novartis; Lilly; Amarin

Speaker’s BureauBoehringer Ingelheim

Grant/Research SupportNIH

Editorial BoardsCirculation (Associate Editor)