Novartis shelves potential blockbuster pelacarsen as landmark study fails

 Novartis AG is largely abandoning the development of its experimental cardiovascular drug pelacarsen, once projected to be a multi-billion-dollar blockbuster, after full study data showed it failed to reduce heart attacks, strokes, or cardiovascular deaths despite drastically lowering a key form of cholesterol. 

The Swiss drugmaker said on Saturday it will halt development of the injectable therapy for atherosclerotic cardiovascular disease, the overarching condition behind heart attacks and strokes. Novartis will keep only a single mid-stage clinical study active to evaluate whether the drug can slow calcific aortic valve stenosis, a heart valve calcification disorder.

The decision follows the long-awaited presentation of detailed findings from the landmark Lp(a) HORIZON trial on Saturday at the American Heart Association scientific sessions in Chicago, alongside simultaneous publication in the New England Journal of Medicine.

The trial results deal a major blow to an experimental class of therapies targeting lipoprotein(a), or Lp(a)—a genetically inherited, cholesterol-carrying particle that promotes arterial clotting and plaque accumulation. While pelacarsen successfully drove down circulating Lp(a) levels by an average of 78%, the reduction generated zero clinical benefit in curbing cardiovascular events across every subgroup tested.

’Stone cold neutral’

"The trial is completely neutral," said Dr. Steven Nissen, chief academic officer at the Cleveland Clinic’s Heart, Vascular & Thoracic Institute and senior author of the study to Bloomberg.

"It is not harmful. It is not helpful. It is just stone cold neutral."

Novartis’s seven-year trial, which enrolled 8,322 patients with pre-existing cardiovascular disease and elevated Lp(a), was the first Phase 3 cardiovascular outcomes study in the industry to reach completion for this biological pathway.

Cardiologists and Wall Street analysts had broadly anticipated that clearing the particle would establish an entirely new pillar of preventive heart medicine, filling a major treatment void for the estimated 20% of the global population with high genetic levels unresponsive to statins or lifestyle modifications.

The medical community was left blindsided in September when Novartis issued a brief statement disclosing that the trial had missed its primary endpoints, withholding granular data until Saturday’s medical congress.