Experimental Drug Pelacarsen Fails to Reduce Heart Attack Risk Despite Lowering Lipoprotein Levels
An experimental drug significantly reduced lipoprotein(a) levels but failed to prevent major cardiovascular events in a large clinical trial, prompting its discontinuation.
A clinical trial evaluating the experimental drug pelacarsen showed a 78% reduction in lipoprotein(a) levels after one year of treatment. Despite this dramatic drop in the particle associated with cardiovascular disease risk, a five-year follow-up of 8,322 patients who had already suffered a cardiovascular event revealed no significant difference in major adverse cardiac events between the treatment and placebo groups, according to findings presented at the American Heart Association conference in Chicago.
Disappointing Trial Results and Novartis Decision
Pelacarsen, developed by Novartis and Ionis, belongs to a class of medications known as antisense oligonucleotides, which target messenger RNA in liver cells to reduce the production of the protein required for lipoprotein(a) formation. The trial, published in The New England Journal of Medicine, tracked participants over a median of 4.7 years. Severe events occurred in 12.3% of the pelacarsen group compared to 12.1% in the placebo group. Following these results, Novartis announced the termination of its development program for pelacarsen in atherosclerotic cardiovascular disease.
Broader Challenges in Cardiovascular Research
At the same conference, disappointing results were presented regarding another experimental therapy, ziltivekimab, developed by Novo Nordisk. Aimed at neutralizing interleukin-6 to combat systemic inflammation in high-risk heart disease patients, the drug successfully reduced inflammation markers but failed to lower the risk of death, heart attack, or stroke compared to placebo. Consequently, Novo Nordisk halted advanced trials for the drug.
Clinical Guidance and Future Outlook
Despite the setback, major medical organizations recently recommended that all adults measure their lipoprotein(a) levels at least once in their lifetime, as levels remain relatively stable. Medical experts emphasize that knowing these levels helps optimize management of traditional risk factors such as smoking cessation, physical activity, blood pressure control, and LDL cholesterol reduction. Other experimental therapies utilizing different mechanisms to achieve even greater reductions in lipoprotein(a) are currently undergoing clinical trials, with results expected in the coming years.
