An experimental medicine that doctors hoped would become a major advance in preventing heart attacks and strokes failed a crucial clinical test, according to researchers who presented the findings Saturday. The drug, known as pelacarsen, successfully reduced levels of a specific blood particle linked to cardiovascular disease, but that reduction did not translate into fewer heart complications for patients.
Steven Nissen, a cardiologist at the Cleveland Clinic who led the study, said he was surprised by the outcome. “I was shocked. I had high hopes for success,” Nissen said. “Cardiovascular disease is still the leading cause of death in developed countries. And so we really were hoping to find additional therapies that would reduce risk.”
Study Results and Patient Profile
The research focused on a group of patients who appeared to follow all standard medical advice. These individuals maintained low cholesterol and blood pressure, ate healthy diets, kept a healthy weight, and exercised regularly. Despite these efforts, many still suffered heart attacks and strokes. A common factor among these patients was elevated levels of lipoprotein(a), or Lp(a), a cholesterol-carrying protein that has long been associated with increased heart disease risk.
Nissen noted that about 20% of the global population has elevated Lp(a) levels, affecting roughly one billion people. Until recently, physicians lacked effective treatments to lower these levels. Several pharmaceutical companies have developed experimental medications in recent years capable of significantly reducing Lp(a).
For the pelacarsen trial, Nissen and his colleagues enrolled 8,350 adults with existing heart disease. Participants were randomly assigned to receive either a placebo or the experimental drug. The study showed that pelacarsen suppressed Lp(a) levels by approximately 78%. However, after five years of monitoring, the drug did not protect volunteers from suffering cardiovascular complications.
Nissen described the results as “very disappointing, terribly disappointing.” He presented the initial details at an American Heart Association meeting in Chicago and published the full specifics in the New England Journal of Medicine and NEJM Evidence. Novartis, the drugmaker that sponsored the study, announced last month that the trial had not met its primary goals but did not release specific data at that time.
Expert Reactions and Future Directions
The failure of pelacarsen is particularly striking given the high expectations within the medical community. Many scientists and doctors believed that Lp(a)-lowering drugs would provide the next significant tool in the fight against cardiovascular disease, which kills more than 900,000 Americans annually. Harlan Krumholz, a cardiologist at Yale University, said the result was jarring because the expectation for a positive outcome was so strong.
Novartis stated in a release that the study provides “meaningful evidence” regarding the relationship between Lp(a) and heart disease. The company added that progress in science depends on pursuing challenging questions and that studies like this play a role in moving the field forward, even when results are not as hoped.
Researchers are now examining why the drug failed to deliver clinical benefits despite lowering the target protein. Roger Blumenthal, a cardiologist at Johns Hopkins University, suggested that patients might need to be treated for a longer duration or earlier in the disease process, before advanced hardening of the arteries occurs.
David Maron, president of the American Society of Preventive Cardiology and a cardiologist at Stanford University, proposed that the drug might only help individuals with higher baseline Lp(a) levels. He suggested that a higher threshold for Lp(a) should have been required for entry into the trial. Other experts noted that the drug might only benefit patients whose blood pressure and bad cholesterol were not well controlled, or that there may be specific characteristics of pelacarsen that prevent it from producing a benefit.
Other pharmaceutical companies, including Amgen and Eli Lilly, are currently testing different experimental Lp(a)-lowering drugs. Results from those trials are expected to emerge over the next few years. Karol Watson, a cardiologist at the University of California, Los Angeles, emphasized that the story is not over. “The take-home message is the story’s not over,” Watson said. “It’s kind of just starting.”
Source: NPR
