Novartis trial failure raises stakes for Amgen and Eli Lilly in Lp(a) drug

Novartis‘ failure in a closely watched cardiovascular trial has raised questions about one of the pharmaceutical industry’s biggest drug races and rival treatments from U.S. heavyweights Amgen and Eli Lilly.

The pelacarsen drug, developed jointly with Ionis Pharmaceuticals, reduced a particularly harmful form of cholesterol in a late-stage clinical trial, but failed to significantly improve cardiovascular outcomes, Novartis said after the bell on Friday. The stock fell 3% on Monday.

It is the first major clinical setback in the race to develop treatments that lower Lp(a), which elevates cardiovascular risks that are estimated to affect roughly one in five people worldwide and for which there is currently no approved targeted treatment.

Although Amgen and Lilly are testing different technologies that have been shown to produce deeper reductions in the cholesterol called Lp(a), analysts say pelacarsen’s failure raises the risk around a market that market watchers expect to be worth billions of dollars.

“The Lp(a) hypothesis is weakened, but not disproven,” Citi analysts said in a research note, noting that details remain scarce beyond the topline miss, including the magnitude by which pelacarsen lowered Lp(a) levels.

More data is needed to determine whether the miss reflects pelacarsen’s mechanism, trial design, or a challenge to the whole hypothesis that lowering Lp(a) can reduce heart attacks and strokes, they added. 

Novartis said full results would be presented at an upcoming medical congress. The company’s chief medical officer, Shreeram Aradhye, said they “provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management.”

Lp(a), short for lipoprotein(a), was discovered in 1963 and can contribute to the buildup of plaque in arteries and blood clotting. Nearly 50 years after its discovery, researchers found that people with elevated Lp(a) levels faced more than twice the risk of a heart attack.

A person’s Lp(a) levels are determined almost entirely by genetics and, unlike LDL cholesterol, are largely unaffected by lifestyle changes such as diet and exercise. 

Novartis emphasized that the more than 8,000 patients in the trial were already on optimized care, while Jefferies analysts said in a Sunday note that improving standards of care are reducing cardiovascular events, potentially making it harder and more costly for experimental drugs to prove an added benefit in clinical trials.