Ionis-partnered pelacarsen missed its primary endpoint in the Lp(a)HORIZON outcomes study, failing to reduce cardiovascular death, heart attacks, strokes or urgent revascularization versus placebo. The drug lowered Lp(a) levels substantially but without clinical benefit, and Novartis shares dropped 4.4 percent after hours.
A closely watched cardiovascular drug developed by Ionis Pharmaceuticals failed its pivotal Phase 3 test, dealing a blow to the Lp(a)-lowering drug class and to Ionis's partner Novartis, which licensed the medicine in 2019.
"Although pelacarsen substantially lowered Lp(a) levels consistent with previous studies, we are disappointed that this did not translate to cardiovascular risk reduction," Brett P. Monia, chief executive officer at Ionis, said.
The Lp(a)HORIZON study enrolled 8,323 patients with elevated Lp(a) and established cardiovascular disease, randomizing them to pelacarsen or placebo. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization. The drug demonstrated an acceptable safety profile, and full data will be presented at an upcoming medical congress.
Novartis shares fell 4.4 percent to $153.00 in after-hours trading Friday. Ionis, which discovered pelacarsen and conducted early development before Novartis exercised its option in February 2019, did not disclose its share reaction.
Elevated Lp(a) is an inherited, causal cardiovascular risk factor affecting approximately one in five people worldwide, with no approved targeted treatment. Trial participants received guideline-directed care including lipid-lowering and antihypertensive therapies.
"These are not the results we hoped for, but they provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes," Shreeram Aradhye, chief medical officer at Novartis, said.
The miss raises questions about the Lp(a)-lowering hypothesis and the commercial value of the Ionis-Novartis partnership. For Ionis, the setback comes as the company pushes forward with independent commercialization of its wholly owned medicines — Tryngolza, Dawnzera and Zanvastro, which received FDA approval for Alexander disease on Sept. 3. Full Lp(a)HORIZON data will be presented at an upcoming medical congress, and investors will watch for Ionis's next pipeline readouts in cardiometabolic disease.
This article is for informational purposes only and does not constitute investment advice.
