Novartis Halts Lp(a) Heart Drug Pelacarsen After Pivotal Trial Shows No Benefit

Novartis will halt development of pelacarsen, its experimental lipoprotein(a) drug, for atherosclerotic cardiovascular disease after full results from the Lp(a)HORIZON trial showed no benefit, according to Investing.com. The data were presented Saturday, Nov. 7, as a late-breaking study at the American Heart Association Scientific Sessions in Chicago and published in the New England Journal of Medicine. Novartis had disclosed in September that the trial missed its primary endpoint. Investing.com reports one mid-stage study in calcific aortic valve stenosis will continue.

The trial enrolled 8,323 patients with established cardiovascular disease and elevated Lp(a). Pelacarsen lowered Lp(a) by a mean of 78%, but the primary composite of heart attack, stroke, urgent revascularization and cardiovascular death occurred in 12.3% of the pelacarsen group and 12.1% of the placebo group, a hazard ratio of 1.02 (95% confidence interval 0.90 to 1.15). Senior author Steven Nissen of the Cleveland Clinic called the result "stone cold neutral" in comments reported by Investing.com. William Blair had estimated $6 billion in peak annual U.S. sales had it succeeded.

The result raises questions for the wider class. AMGN is developing olpasiran and LLY is developing lepodisiran, both injectable siRNA drugs rather than the antisense approach used by pelacarsen, and Nissen said siRNA drugs may cause fewer injection-site reactions. Amgen's olpasiran reduced Lp(a) by more than 95% in mid-stage testing, and William Blair has suggested deeper Lp(a) lowering may offer an opportunity.

Investors may watch the remaining Lp(a) outcome trials for evidence on whether deeper lowering or different patient selection changes the result, and how NVS reallocates cardiovascular resources. No Lp(a)-lowering therapy is approved.