Silence Therapeutics has announces positive topline 36-week data from its ongoing Phase 2 Study of Zerlasiran in patients with high Lipoprotein(a), reporting that the study met the primary endpoint and demonstrated highly significant reductions in Lp(a) to week 36. Image courtesy: Silence Therapeutics
March 13, 2024 — Silence Therapeutics has announced positive topline 36-week data from the ongoing ALPACAR-360 phase 2 study of zerlasiran (SLN360) in 178 subjects with baseline lipoprotein(a), or Lp(a), levels at or over 125 nmol/L at high risk of atherosclerotic cardiovascular disease (ASCVD) events. 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.
In the double-blind placebo-controlled treatment period, zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nmol/L. These data demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo to 36 weeks (primary endpoint), according to a written statement released today on the outcomes. Median percentage reduction in Lp(a) of 90% or greater were observed for both doses at week 36. No new safety concerns were identified during this treatment period.
The 60-week study is ongoing and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period), 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.
The company describes Zerlasiran as a gene ‘silencing’ therapy designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. In this case, it aims to ‘silence’ LPA, a gene that tells the body to make a specific protein that is only found in Lp(a). By silencing the LPA gene, the levels of Lp(a) are lowered, which in turn is expected to lower the risk of heart diseases, heart attacks and strokes.
“We are excited about the emerging phase 2 data, which are very consistent with phase 1 results and support a competitive profile for treating patients with high Lp(a),” said Steven Romano, MD, Head of Research and Development at Silence. “We look forward to reviewing the 48-week data and advancing zerlasiran as a potential treatment to address this major unmet need in cardiovascular disease,” Romano added.
Silence plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year, according to the written statement issued today by the London-based biotech company which develops precision engineered medicines.
The company highlighted the significance of the study, reinforcing that cardiovascular disease is the number one cause of death and disability worldwide. A major risk factor for cardiovascular disease is a high blood level of low-density lipoprotein cholesterol (LDL-C), or “bad cholesterol,” that can be treated with statins. However, statins cannot treat people who have elevated blood levels of lipoprotein(a), or Lp(a), a genetic risk factor that affects approximately 20 percent of the world’s population. It added that, although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing, including zerlasiran (SLN360), a short interfering RNA (siRNA) designed to lower the body’s production of Lp(a).
More information: www.silence-therapeutics.com
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