Silence Therapeutics’ Zerlasiran Shows LP(a) Potential

Silence Therapeutics’ zerlasiran continued to demonstrate its lipoprotein(a) impact, as topline Phase 2 data showed that the injectable siRNA slashed LP(a) levels by over 90% through 36 weeks.

  • Zerlasiran is a siRNA (short interfering RNA), designed to reduce LP(a) levels by “silencing” the LPA gene that tells the body to make the apolipoprotein(a) protein. 
  • LP(a) is a common and potentially significant cardiovascular disease risk factor, although LP(a)-lowering therapy options are currently limited.

The double-blind placebo-controlled ALPACAR-360 study subcutaneously administered 300mg of zerlasiran every 16 or 24 weeks or 450 mg every 24 weeks to 178 patients with a median baseline Lp(a) of 215 nmol/L who are at high risk of atherosclerotic cardiovascular events.

  • After 36 weeks, both doses saw 90% or greater median Lp(a) reductions compared to placebo, while revealing no new safety concerns.

Those results closely match zerlasiran’s Phase 1 trial, which found that patients who received 450mg doses saw a 99% reduction in Lp(a) levels at 90 days, which stabilized at a 90% reduction by 201 days.  

Zerlasiran’s initial Phase 1 and Phase 2 results could be further validated as the ALPACAR-360 study continues, including 48-week data that will show LP(a) reductions through the end of the treatment period and 60-week data that includes post-treatment and secondary endpoints.

The ALPACAR-360 study also adds to the growing evidence supporting siRNA’s potential for LP(a) reduction.

  • Amgen’s injectable siRNA olpasiran slashed Lp(a) by as much as 100% in its Phase II trial, and has moved on to Phase III.
  • Lilly’s injectable siRNA lepodisiran drove more than 90% LP(a) reductions that lasted almost a year in its recent Phase 1 study.
  • Meanwhile, Lilly’s small molecule inhibitor muvalaplin also performed well in its Phase I trial, reducing LP(a) levels by up to 65%, and bringing 93% of participants below 50 mg/dL.

The Takeaway

Although zerlasiran still has plenty to prove, its Phase 1 and 36-month Phase 2 results suggest that it has the potential to be a powerful LP(a)-reducing option, adding to the massive momentum we’re seeing across the siRNA segment.

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