The pelacarsen Phase 3 trial did not meet its primary endpoint of reducing major cardiovascular events in patients with elevated lipoprotein(a) and established cardiovascular disease.
Novartis (NYSE: NVS) said the Lp(a)HORIZON study failed to show a reduction in a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization requiring hospitalization compared with placebo. The result was disclosed in the company’s official topline announcement.
Pelacarsen substantially lowered Lp(a) levels, consistent with earlier studies, but the biomarker improvement did not translate into the required clinical-outcome benefit. Participants also received guideline-directed treatments, including lipid-lowering and antihypertensive therapies.
Pelacarsen Phase 3 Trial Challenges Lp(a) Treatment Thesis
The randomized, double-blind study enrolled 8,323 patients and evaluated the primary endpoint in the overall population and a subgroup with higher Lp(a) levels. Novartis has not yet released the complete study dataset.
Ionis Pharmaceuticals (Nasdaq: IONS) developed the antisense medicine and licensed it to Novartis, which is responsible for development and potential commercialization. Elevated Lp(a) affects roughly one in five people worldwide, and no targeted treatment has been approved.
The failed primary endpoint weakens the program’s regulatory and commercial prospects, but the full implications will depend on detailed efficacy, subgroup and safety results. Novartis said the findings add evidence to the scientific understanding of Lp(a) lowering and cardiovascular outcomes.
