Novartis Lp(a) Failure Casts Shadow on Cardiovascular Drug Race

Key points

• Novartis announced that pelacarsen, developed with Ionis Pharmaceuticals, failed to meet its primary endpoint in a Phase III trial involving over 8,000 patients with established cardiovascular disease.
• The drug successfully reduced Lp(a) levels by approximately 80%, but did not significantly lower the rates of heart attack, stroke, or cardiovascular death.
• The failure follows recent setbacks for Novo Nordisk’s ziltivekimab in cardiovascular and chronic kidney disease trials, creating a 'chilling effect' on industry investment.
• Analysts from Citi and Jefferies note that while the Lp(a) hypothesis is weakened, it is not disproven, as other companies like Amgen and Eli Lilly are testing drugs with different mechanisms that may achieve deeper reductions.
• Novartis shares fell 3% after the news, while Ionis dropped 10% and Amgen fell 5% in extended trading, reflecting investor anxiety over the broader market for Lp(a) treatments.

Background

This development follows a series of setbacks in the cardiovascular space. In July 2026, Novo Nordisk reported that its anti-inflammatory drug ziltivekimab failed to reduce major adverse cardiovascular events in patients with chronic kidney disease. Additionally, Novo Nordisk suffered a Phase 3 setback for a cardiovascular inflammation drug in August 2026. These consecutive failures have heightened scrutiny on the industry's reliance on new biomarkers for heart disease treatment.

How outlets are covering it

STAT highlights the potential for a 'chilling effect' on the industry, with cardiologist Ethan Weiss suggesting the failures could 'pop a hole in the balloon' of the field, making future investments harder. The New York Times emphasizes the scientific confusion, noting that cardiologists are struggling to understand why a drug that effectively lowered Lp(a) did not prevent heart attacks, questioning if Lp(a) is merely a marker rather than a cause. CNBC focuses on the financial implications, noting that while the hypothesis is weakened, competitors like Amgen and Eli Lilly may still succeed with different technologies that achieve deeper Lp(a) reductions. Citi analysts caution that details remain scarce, and the failure may reflect trial design or mechanism-specific issues rather than a fundamental flaw in the Lp(a) theory.

Why it matters

The failure of pelacarsen, which was projected to generate $4-5 billion in peak annual sales, threatens to disrupt Novartis’s pipeline as it faces a significant patent cliff. More broadly, it raises questions about the billions of dollars invested in Lp(a) therapies by multiple companies, potentially reshaping the future of cardiovascular drug development and investment strategies.

What to watch

Novartis will present full trial data at an upcoming medical congress. Investors and analysts will closely watch the results of Amgen’s olpasiran and Eli Lilly’s lepodisiran trials to determine if different mechanisms can achieve the clinical benefits that pelacarsen failed to deliver. The outcome of these trials will likely determine whether the Lp(a) drug class remains a viable therapeutic area.