NEW YORK – Silence Therapeutics on Thursday said top-line data from its ongoing Phase II clinical trial of the experimental cardiovascular drug zerlasiran supports advancing the drug into a Phase III clinical trial at a dose of 300 milligrams.
London-based Silence Therapeutics is studying zerlasiran within a randomized-controlled Phase II clinical trial dubbed ALPACAR-360, which enrolled patients at high risk of atherosclerotic cardiovascular disease events and elevated lipoprotein(a), a type of low-density lipoprotein cholesterol that's associated with cardiovascular diseases.
Patients received a placebo or zerlasiran every 16 weeks or 24 weeks for a 48-week treatment period. Zerlasiran, an siRNA therapy, targets and degrades the mRNA that encodes for one of Lp(a)'s core components, apolipoprotein(a).
Zerlasiran-treated patients experienced sustained reductions in Lp(a) from baseline compared to the group that received a placebo through week 48. The median maximum Lp(a) reduction was about 90 percent or greater and was observed for the two doses that investigators studied in the clinical trial, 300 milligrams or 450 milligrams.
Zerlasiran was tolerated well, and investigators observed no serious safety concerns. Patients will continue to be monitored through week 60.
The Phase II data suggest "an infrequent dosing regimen of at least quarterly with the 300 milligram dose," Steven Romano, Silence Therapeutics' head of R&D, said in a statement. "We look forward to advancing zerlasiran to Phase III as a potential treatment for this major unmet need in cardiovascular disease."
Silence Therapeutics leadership previously said the company expects to launch a registrational Phase III trial in 2025, in which investigators will track cardiovascular outcomes on zerlasiran.
There are multiple investigational drugs targeting Lp(a) in clinical trials, including candidates from Novartis Pharmaceuticals, Amgen, and Eli Lilly, but none have been approved for marketing.