An experimental cholesterol-lowering drug developed by Novartis failed to reduce heart attacks, strokes, or cardiovascular deaths in a large clinical trial, despite significantly lowering a dangerous form of cholesterol.
The drug, pelacarsen, was designed to target lipoprotein(a) [Lp(a)], a genetic form of cholesterol linked to increased risk of cardiovascular events. In the Horizon trial, which included 8,322 participants with high Lp(a) levels and a history of heart disease, pelacarsen reduced Lp(a) by 78% compared to a 13% reduction in the placebo group. However, the trial found no measurable difference in the rates of heart attacks, strokes, cardiovascular deaths, or procedures to restore blood flow to the heart.
Key findings from the trial:
- Pelacarsen reduced Lp(a) levels by 78%, a statistically significant drop.
- No reduction in cardiovascular events was observed over the study period.
- The trial enrolled participants who had already experienced a heart attack, stroke, or other cardiovascular event within the past 10 years.
Researchers expressed disappointment, noting that the drug’s failure represents a setback for preventive cardiology. Dr. Amanda Doran, an assistant professor of medicine at Vanderbilt University Medical Center and a trial investigator, stated, “I really thought that this was going to be a slam dunk. We were pretty invested, so it obviously hurts.”
About Lp(a) and its risks:
- Lp(a) is a genetic form of cholesterol that contributes to plaque buildup in arteries and increases the risk of blood clots.
- Approximately 1 in 5 Americans have high Lp(a) levels, though most are unaware of their risk.
- Unlike LDL cholesterol, Lp(a) levels are not affected by diet or exercise, making medication the only potential intervention.
The Horizon trial, presented at the American Heart Association meeting, was one of the largest and most closely watched studies evaluating a drug targeting Lp(a). The results underscore the challenges of translating biochemical reductions into clinical benefits.
What’s next for pelacarsen?
Novartis has not announced whether further development of pelacarsen will continue. The company has not responded to requests for comment on the trial’s outcome. Researchers emphasize that the failure does not rule out future success for other drugs targeting Lp(a), as multiple experimental treatments remain in development.
Broader implications for heart disease treatment:
The trial highlights the complexity of cardiovascular disease prevention, particularly for patients who maintain healthy lifestyles but still face elevated risks due to genetic factors. While pelacarsen’s failure is a setback, experts note that research into Lp(a)-lowering therapies will likely continue, given the large population affected by high Lp(a) levels worldwide.