Novartis heart drug fails major trial, casting doubt on cholesterol class

Novartis ↘ 1.90% announced on Friday that its experimental drug pelacarsen failed to reduce the risk of major cardiovascular events in the Phase 3 Lp(a)HORIZON trial, dealing a blow to the Swiss drugmaker's pipeline and raising questions about an entire class of heart drugs in development.novartis+1

A Pioneering Trial Falls Short

The trial, which ran for more than six years and enrolled over 8,300 patients with elevated levels of lipoprotein(a) — a genetically inherited cholesterol particle linked to higher heart risk — was the first late-stage study to test whether lowering Lp(a) could prevent heart attacks, strokes, and cardiovascular death. While pelacarsen did lower Lp(a) levels consistent with earlier studies, that reduction did not translate into fewer cardiac events compared to placebo.statnews+3

"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," said Novartis chief medical officer Shreeram Aradhye. Ionis Pharmaceuticals ↘ 0.07% CEO Brett Monia said the company was "disappointed that this did not translate to cardiovascular risk reduction".reuters+1

Ripple Effects Across the Industry

U.S.-listed shares of Novartis fell 5% in after-hours trading on Friday, while Ionis dropped 12%. Amgen ↘ 1.55%, which is developing a rival Lp(a)-lowering drug called olpasiran, also saw shares decline 5% after hours. Eli Lilly ↘ 0.88% has its own Lp(a) drug, lepodisiran, in late-stage development. Both rival programs now face heightened scrutiny.reuters+1

Citi analyst Geoff Meacham noted that full trial data are needed to determine whether the failure reflects the drug's mechanism, insufficient Lp(a) reduction, trial design issues, or fundamental doubts about the Lp(a) hypothesis. "The first dedicated outcomes failure lowers confidence across the class," Meacham said.kelo

What's Next for Novartis

The failure comes at a difficult time for Novartis as it faces steep patent expiries and the loss of revenue from blockbuster heart drug Entresto. Investors had viewed pelacarsen alongside anti-inflammatory drug remibrutinib and gene therapy del-desiran as potential drivers of more than $10 billion in combined peak annual sales. Earlier in the week, remibrutinib succeeded in a late-stage multiple sclerosis study, with analysts projecting up to $9 billion in peak annual sales for that drug alone. The companies said full pelacarsen trial data will be presented at an upcoming medical congress.Reuters+2