Silence Therapeutics Reports Further Phase 1 Zerlasiran Trial Results in JAMA for Patients with High Lipoprotein(a)

New findings reveal that zerlasiran, an innovative therapeutic developed by Silence Therapeutics plc, effectively reduces lipoprotein(a) (Lp(a)) levels and is well-tolerated in both single and multiple doses. Published in the Journal of the American Medical Association (JAMA), the APOLLO phase 1 study focused on subjects with baseline Lp(a) levels of 150 nmol/L or higher.

Zerlasiran, a short interfering RNA (siRNA), targets and reduces the body's production of Lp(a), a significant genetic risk factor for cardiovascular disease, affecting up to 20% of the global population. The study included 32 healthy participants and 36 patients with atherosclerotic cardiovascular disease (ASCVD) and elevated Lp(a) levels.

In the single ascending dose trial, healthy participants were administered either a placebo, 300 mg, or 600 mg dose of zerlasiran. ASCVD patients received two doses at varying intervals: placebo, 200 mg at 4-week intervals, or 300 mg or 450 mg at 8-week intervals. Safety and tolerability were the primary outcomes, while secondary outcomes assessed serum levels of zerlasiran and its impact on Lp(a) concentrations.

Results showed that zerlasiran was safe and well-tolerated. In healthy participants, median Lp(a) levels changed by +14% for placebo, −30% for 300 mg, and −29% for 600 mg over 365 days. For ASCVD patients, the maximal median changes after two doses were +7% for placebo, -97% for 200 mg, -98% for 300 mg, and -99% for 450 mg, with effects diminishing to 0.3%, -60%, -90%, and -89% respectively after 201 days.

Currently, zerlasiran is being tested in the ALPACAR-360 phase 2 study for subjects with baseline Lp(a) levels of 125 nmol/L or higher, who are at high risk of ASCVD events.

Silence Therapeutics continues to develop RNA interference (RNAi) therapies, aiming to address significant unmet medical needs. Their proprietary mRNAi GOLD™ platform creates siRNAs targeting disease-associated genes. Other product candidates include divesiran for hematological diseases like polycythemia vera. The company also collaborates with AstraZeneca and Hansoh Pharma.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!