Silence Therapeutics Announces JAMA Publication of Additional Phase 1 Data for Zerlasiran in Subjects with Elevated Lipoprotein(a)

Silence Therapeutics plc, Nasdaq: SLN (“Silence” or the “Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today announced additional results from the APOLLO phase 1 study of zerlasiran (SLN360) in subjects with baseline lipoprotein(a), or Lp(a), levels at or over 150 nmol/L were published in the Journal of the American Medical Association (JAMA), linked here.

Zerlasiran is a siRNA (short interfering RNA) designed to lower the body’s production of Lp(a), a key genetic risk factor for cardiovascular disease affecting up to 20% of the world’s population.

“Positive phase 1 data published in JAMA demonstrate treatment with zerlasiran produced sustained reductions in Lp(a) concentrations with a well-tolerated profile using varying dosing regimens,” said Curtis Rambaran, MD, Chief Medical Officer at Silence and senior author of the publication. “The promising findings from this study are particularly encouraging as we complete the phase 2 study for zerlasiran and underscore our commitment to address this major unmet need in cardiovascular disease.”

The single ascending and multiple dose trial enrolled 32 healthy participants and 36 patients with atherosclerotic cardiovascular disease (ASCVD) and Lp(a) concentrations ≥150 nmol/L. Results from the single ascending dose portion of the trial in healthy participants were previously published in the April 2022 issue of JAMA, linked here. Today’s JAMA publication reviews findings from the extended 365 day follow up of healthy participants who received the two highest zerlasiran doses (300 or 600 mg) and 201 days of follow up for ASCVD patients administered 2 doses.

Healthy participants were randomized and received a single subcutaneous dose of placebo, 300 mg or 600 mg; ASCVD patients received two doses of placebo, 200 mg at a 4-week interval or 300 mg or 450 mg at an 8-week interval. The primary outcome was safety and tolerability. Secondary outcomes included the serum levels of zerlasiran and effects on Lp(a) serum concentrations.

Zerlasiran was safe and well tolerated. The median change from baseline in serum Lp(a) concentrations 365 days after single doses for placebo, 300 mg, and 600 mg were +14%, −30%, and −29% respectively. The maximal median change from baseline after two doses of placebo, 200 mg, 300 mg and 450 mg were +7%, -97%, -98% and -99%, attenuating to 0.3%, -60%, 90% and 89% respectively, after 201 days.