A highly anticipated experimental drug, pelacarsen, which reduces levels of a particle in the blood associated with heart attacks and strokes, has failed to protect volunteers in a closely watched study. The study, led by cardiologist Steven Nissen of the Cleveland Clinic, involved 8,350 adults with heart disease who were given either the drug or a placebo. Despite reducing levels of the particle by 78%, the drug did not translate into saving people from suffering cardiovascular complications.
The study aimed to help people who seem to do everything right to prevent heart disease but still suffer heart attacks and strokes. These patients often have elevated blood levels of a cholesterol-carrying protein called lipoprotein(a) or Lp(a), which is thought to increase the risk of heart disease. About 20% of the global population has elevated levels of Lp(a), making it a common disorder. Researchers have been searching for a drug to lower Lp(a) levels, and several companies have developed experimental medications in recent years.
The failure of pelacarsen to help patients is surprising, as many scientists, doctors, and drug companies had high hopes that Lp(a)-lowering drugs would provide the next major weapon in the fight against cardiovascular disease. Cardiovascular disease is the leading cause of death in developed countries, and researchers were hoping to find additional therapies to reduce risk. The study's failure has left researchers scratching their heads, wondering what went wrong.
One possibility is that high Lp(a) levels may not actually cause heart attacks and strokes but instead are a marker for something else that increases the risk. Other explanations could be that the study population may not have had high enough Lp(a) levels or that the treatment duration was too short. The study's results may also suggest that Lp(a)-lowering drugs may only benefit people with higher Lp(a) levels or those with less well-controlled blood pressure and bad cholesterol.
Despite the disappointing results, researchers emphasize that the study provides meaningful evidence about the relationship between Lp(a) and heart disease. The study's findings may help inform future approaches to cardiovascular management. Novartis, the drugmaker that sponsored the study, stated that the results "provide meaningful evidence" and may "help inform future approaches to cardiovascular management."
The failure of pelacarsen does not necessarily mean that other Lp(a)-lowering drugs will not be effective. Several other drugmakers, including Amgen and Eli Lilly, are testing experimental Lp(a)-lowering drugs, and the results of those trials are expected to become available over the next few years. Cardiologist Karol Watson of the University of California, Los Angeles, notes that "the take-home message is the story's not over; it's kind of just starting."
The study's findings have significant implications for the development of new treatments for heart disease. As cardiologist Harlan Krumholz of Yale University noted, the failure of pelacarsen was "really jarring" given the high expectations for the drug. However, researchers remain optimistic that future studies will shed more light on the relationship between Lp(a) and heart disease and ultimately lead to the development of effective treatments.
Key points
- The experimental drug pelacarsen failed to show benefits in a large study despite reducing levels of a particle in the blood associated with heart attacks and strokes.
- The study's failure has significant implications for the development of new treatments for heart disease and highlights the complexity of the relationship between Lp(a) and cardiovascular risk.
- Other Lp(a)-lowering drugs are currently being tested, and the results of those trials are expected to become available over the next few years.
