Nov. 18, 2024 — Silence Therapeutics presented end-of-treatment data from its Phase 2 ALPACAR-360 study of zerlasiran, a short interfering RNA (siRNA), in atherosclerotic cardiovascular disease (ASCVD) patients with high lipoprotein(a) [Lp(a)] levels (≥125 nmol/L).
These data were presented at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, Illinois, and simultaneously published in the Journal of the American Medical Association (JAMA).
Results presented today showed that zerlasiran (300 mg every 16 weeks, 300 mg every 24 weeks or 450 mg every 24 weeks) produced greater than 80% mean time-averaged placebo-adjusted reductions from baseline in Lp(a) concentrations over 36 weeks. This is the first study to report time-averaged Lp(a) analyses, which more accurately evaluates the effects of treatment over time, including intervals between doses. Maximum Lp(a) reductions exceeded 90%. At the final visit, 60 weeks following initial drug administration, reductions in Lp(a) persisted and no safety concerns emerged with infrequent dosing.
“These data provide additional information to select the best dose and dosing interval for future zerlasiran Phase 3 trials,” said Steven E. Nissen, MD, Chief Academic Officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic and the study’s lead author. “Elevated Lp(a) impacts at least 20% of the global population and is a major cause for morbidity and mortality globally. This is a genetic risk factor that we’ve been unable to treat and I’m excited about the potential for gene-silencing approaches to help these patients.”
“Additional results from the ALPACAR-360 study continue to support the competitive profile of zerlasiran on key clinical endpoints assessing time-averaged reduction, maximum effect and tolerability,” said Curtis Rambaran, MD, Chief Medical Officer at Silence. “The Phase 2 data show zerlasiran has the potential to provide long term reductions in Lp(a) with infrequent dosing. We look forward to progressing zerlasiran into Phase 3 as a potentially promising new treatment for patients with high Lp(a).”
For more information, please visit https://www.silence-therapeutics.com/.
November 12, 2025 
