Novartis’ failure in a closely watched cardiovascular trial has raised concerns 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.
The stock fell 3% on Monday. It is the first major clinical setback in the race to develop treatments that lower Lp(a), which increases cardiovascular risks that are estimated to affect roughly one in five people worldwide and for which there is currently no approved targeted treatment.
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.
Lp(a) and Cardiovascular Risks
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 raised 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.
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.
Analysts had modelled peak annual sales of around $4 billion to $5 billion for pelacarsen if it proved successful. This would boost Novartis as it faces what CEO Vas Narasimhan has called the steepest patent cliff in its history.
But the trial update’s impact went beyond the company. Shares of Amgen fell about 5% in extended trading on Friday and Ionis Pharmaceutical sank 10%. “The first dedicated outcomes failure lowers confidence across the class and places greater pressure on later studies to demonstrate that deeper lowering can produce a clinically meaningful ~15% [major adverse cardiovascular events] reduction,” the Citi analysts said.
Rival Treatments Face Pressure
Amgen’s competing drug, olpasiran, faces the clearest readthrough, while Lilly’s medicine, lepodisiran, is being trialled on a broader group of patients, including some who have not yet developed established cardiovascular disease, potentially limiting the direct read-through from Novartis’ failure.
Many investors had already viewed the trial as risky and expected only a moderate benefit, which could explain why the Novartis stock reaction was relatively contained, falling only 3% in extended trading on Friday.
As the pharmaceutical industry continues to develop treatments for Lp(a), the failure of pelacarsen may lead to a reevaluation of the approach, with some analysts suggesting that other experimental drugs may be able to reduce Lp(a) more effectively, particularly for patients with very high levels.
William Blair analysts noted that they saw “meaningful risk to a potential future” in Lp(a)-driven trials for cardiovascular diseases in light of Novartis’ results, but also acknowledged that different approaches to lowering Lp(a) may still be successful.
Future of Lp(a) Treatment
The outcome of the trial is a significant development.
Novartis will present full results at an upcoming medical congress.
Researchers will continue to study Lp(a) and its effects on cardiovascular health.
The pharmaceutical industry will likely reassess its approach to developing treatments for Lp(a).
Other companies, such as Amgen and Eli Lilly, will continue to develop their own treatments for Lp(a).
