Novartis Shares Fall 3.3% After Pelacarsen Misses Heart-Risk Goal

Key Facts

Novartis shares fell 3.3% in Monday morning trading after the company said pelacarsen had missed the primary endpoint in the Lp(a)HORIZON study.

The randomized, double-blind Phase 3 trial enrolled 8,323 patients with elevated Lp(a) and established cardiovascular disease. It compared pelacarsen with placebo on top of guideline-directed care.

The primary endpoint measured the drug's ability to reduce a composite of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization. Pelacarsen lowered Lp(a), but that did not translate into reduced cardiovascular risk in the overall study population; Ionis said the safety profile was acceptable.

Pelacarsen is an investigational antisense oligonucleotide designed to inhibit Lp(a) production. Genetics determine about 90% of Lp(a) levels, while roughly 20% of people worldwide have elevated Lp(a), for which no targeted treatment is currently approved.

The miss has financial significance because analysts had estimated peak annual sales of $3 billion to $6 billion. It also raises the evidentiary bar for rival Lp(a)-targeting medicines, including late-stage programs at Amgen and Eli Lilly.

Novartis said the full results will be presented at an upcoming medical congress. Details including effect sizes and subgroup analyses will be important for explaining why lower Lp(a) did not produce a clear clinical benefit in the topline outcome.