November 10, 2023 — Silence Therapeutics plc, an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, announced positive topline results from the multiple dose component of the APOLLO phase 1 study of zerlasiran (formerly SLN360) in 36 adults with baseline lipoprotein(a), or Lp(a), levels at or over 150 nmol/L and stable atherosclerotic cardiovascular disease (ASCVD). 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 approximately 20% of the world’s population.
In the double-blind placebo-controlled treatment period, zerlasiran (200 mg, 300 mg and 450 mg) was administered twice subcutaneously at two different dosing intervals to ASCVD patients. These data demonstrated a significant reduction from baseline in Lp(a) of up to 99% at 90 days following injection of repeated doses. Lp(a) levels remained approximately 90% lower than baseline at 201 days (end of treatment period) at the two highest doses. A dose dependent reduction in low-density lipoprotein cholesterol (LDL cholesterol) and apolipoprotein B (ApoB) was also observed. Zerlasiran was well tolerated; no clinically important safety concerns were identified.
“We are extremely pleased to see the excellent results we saw in healthy volunteers translate to our target population,” said Craig Tooman, President and CEO of Silence. “Zerlasiran delivered essentially complete Lp(a) knockdown on repeated dosing with greater durability than seen with single doses. The safety profile also continues to be very well suited for chronic use in a very large global population. We look forward to building on this dataset with the ongoing phase 2 study expected to readout in the first half of next year.”
Silence plans to present further results from the APOLLO multiple dose study at a future cardiovascular medicines conference.
Results from the single ascending dose portion of the APOLLO study were simultaneously presented in a late breaker at the 2022 American College of Cardiology (ACC) Annual Meeting and published in the Journal of the American Medical Association (JAMA), available here.
Zerlasiran is currently being evaluated in the fully enrolled ALPACAR-360 phase 2 study in patients with Lp(a) levels at or over 125 nmol/L at high risk of ASCVD events. Silence expects to report topline 36-week data in the first quarter of 2024 and topline 48-week data in the second quarter of 2024.
For more information: www.silence-therapeutics.com