Novartis Lp(a) Drug Fails to Prevent Heart Attacks, Shaking Cardiovascular Market

Key points

• Novartis reported that pelacarsen reduced Lp(a) levels by 80% but failed to significantly lower rates of heart attacks or strokes in a large clinical trial.
• The drug was developed in partnership with Ionis Pharmaceuticals and was expected to generate $4 billion to $5 billion in annual sales if successful.
• Shares of Novartis fell 3%, while Ionis dropped 10% and Amgen fell 5% in extended trading following the announcement.
• Analysts note that the failure may be specific to pelacarsen's mechanism, as competitors like Amgen and Eli Lilly are testing drugs that achieve deeper reductions in Lp(a).
• The trial included over 8,000 patients already on optimized care, which may have made it harder to demonstrate additional benefits from the new drug.

Background

Lp(a) is a type of cholesterol discovered in 1963 that contributes to plaque buildup and blood clotting. Elevated levels, determined almost entirely by genetics, increase the risk of heart attack by more than twice. There is currently no approved targeted treatment for high Lp(a), making it a major focus for pharmaceutical companies. The recent failure follows a period of renewed interest in cardiovascular trials, with multiple companies investing billions in Lp(a) therapies.

How outlets are covering it

The New York Times emphasizes the shock among cardiologists and the fundamental question of whether Lp(a) is a marker for another unknown cause of heart disease. STAT highlights the potential chilling effect on the industry, noting that back-to-back failures from Novartis and Novo Nordisk could make investments in the field harder to secure. CNBC focuses on the financial implications for competitors, noting that while the 'Lp(a) hypothesis is weakened, but not disproven,' the failure raises stakes for Amgen and Eli Lilly. Citi analysts suggest the miss may reflect trial design or the specific mechanism of pelacarsen, rather than a flaw in the broader theory that lowering Lp(a) reduces risk. Jefferies analysts point out that improving standards of care may be making it harder for experimental drugs to prove added benefits in clinical trials.

Why it matters

The failure of pelacarsen represents a significant setback in the development of targeted treatments for a major cardiovascular risk factor. It raises questions about the viability of the entire Lp(a) drug class and could impact billions of dollars in investment and future sales projections. The outcome may influence the direction of future clinical trials and the strategies of major pharmaceutical companies in the cardiovascular space.

What to watch

Novartis plans to present full results at an upcoming medical congress, potentially in November. Competitors like Amgen and Eli Lilly will continue their trials, with analysts watching to see if their drugs, which achieve deeper Lp(a) reductions, can demonstrate clinical benefits. The industry will likely reassess the risk and potential of Lp(a) therapies in light of this first major outcomes failure.