Novartis Phase 3 Pelacarsen Trial Misses Cardiovascular Endpoint

Novartis reported that its Phase 3 Lp(a)HORIZON trial of pelacarsen, involving more than 8,000 patients with elevated lipoprotein(a) and established cardiovascular disease, failed to show a significant reduction in major cardiovascular events compared with placebo. Although the investigational antisense drug substantially lowered Lp(a) levels and had an acceptable safety profile, those changes did not translate into fewer cardiovascular deaths, heart attacks, strokes or urgent coronary revascularizations in the overall study population receiving optimized care. The result is a setback for Lp(a)-targeted cardiovascular therapies and for Novartis’ effort to develop new products to offset future patent expirations, though the company and Ionis said the findings will provide important scientific insight and will be presented at a future medical congress. Royalty Pharma said its earlier funding agreement with Ionis was structured to limit the financial impact, allowing it to recoup its investment primarily through Spinraza royalties while avoiding expected pelacarsen milestone payments. The trial’s failure also created potential pressure for Novartis’ valuation, as investors had viewed pelacarsen and other late-stage programs as important contributors to the company’s future growth.