Pharmaceuticals

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.

Get twice-weekly insights on the biggest stories shaping cardiology.

You might also like

Cardiac Imaging June 16, 2025

Beyond Hardware: Is AI the Answer to Making Cardiac Imaging more Accessible? June 16, 2025

Sponsored by Philips Healthcare Cardiac imaging has traditionally improved through hardware advances, enabling the speed needed for high-quality images. However, hardware is rapidly reaching its physical limitations in suppressing cardiac motion and represents a large financial investment. Today, software and AI are driving the next leap in cardiac image quality and motion control – offering […]

Cardiology Pharmaceuticals June 12, 2025

FDA Approves a New BP Triple Polypill June 12, 2025

Bringing a more effective BP therapy to the U.S. market, the FDA approved George Medicines’ triple therapy polypill called Widaplik for patients with hypertension, making it the first of its kind to go to market in the U.S. Widaplik’s approval stems from two studies, including one comparing the polypill against placebo as an initial treatment […]

Cardiology Pharmaceuticals June 12, 2025

Pharmacologic Preconditioning to Improve Outcomes in Patients Undergoing Cardiac Surgery  June 12, 2025

The majority of patients undergoing cardiac surgery, especially those on cardiopulmonary bypass (CPB), experience post-operative complications such as new-onset atrial fibrillation (POAF) and acute kidney injury (AKI), largely driven by oxidative stress and inflammation.   Several approaches have been explored to reduce complications following cardiac surgery, however, a clinically meaningful impact has yet to be realized.  […]

You might also like..

Select All

You're signed up!

It's great to have you as a reader. Check your inbox for a welcome email.

-- The Cardiac Wire Team

You're all set!