pelacarsen Lp(a) heart disease trial failure, Digi Mart USA News: An experimental drug that doctors hoped would be the next big advance in preventing heart attacks and strokes failed a crucial test, researchers reported Saturday. The medicine reduces levels of a blood particle associated with heart attacks and strokes, but it did not protect volunteers in a closely watched study.
Steven Nissen, a cardiologist at the Cleveland Clinic who led the study, said he was shocked by the outcome. “I had high hopes for success,” he 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.”
The research aimed to help people who seem to do everything right. They keep their cholesterol and blood pressure low, eat well, maintain a healthy weight and exercise regularly, yet many still suffer heart attacks and strokes.
“That sort of patient we see very frequently, and we were really doing our best to try to find a way to help those patients,” Nissen said.
Many of these patients have elevated blood levels of a cholesterol-carrying protein called lipoprotein(a), or Lp(a), which has long been thought to increase the risk for heart disease. “About 20% of the global population have elevated levels.
And that’s about a billion people. So it’s a common disorder,” Nissen said.
Until recently, doctors had no drugs that could lower Lp(a) levels. Several drug companies have since developed experimental medications that can sharply reduce elevated Lp(a).
Nissen and his colleagues gave 8,350 adults who already had heart disease either a placebo or pelacarsen, a drug that cuts Lp(a). The drug suppressed Lp(a) levels by about 78%, the researchers showed.
But after five years, that drop did not translate into preventing cardiovascular complications.
“Very disappointing, terribly disappointing,” Nissen said. He presented the first details of the study at an American Heart Association meeting in Chicago on Saturday and published more specifics in the New England Journal of Medicine and NEJM Evidence.
Drugmaker Novartis, which sponsored the study, announced last month that the results had not met its goals but did not release specifics. In a statement, Novartis said the study “provides meaningful evidence” about the relationship between Lp(a) and heart disease and may “help inform future approaches to cardiovascular management.” The company said, “Progress in science depends on pursuing challenging questions and studies [like the pelacarsen study] play a crucial role in moving the field forward, even if the results are not what we had hoped for.”
The failure is striking because so many scientists, doctors and drug companies hoped Lp(a)-lowering drugs would provide the next major weapon against cardiovascular disease, which kills more than 900,000 Americans each year. “I think it’s a big deal because the expectation was so high that this would end up being positive,” said Harlan Krumholz, a Yale University cardiologist.
“And so it was really jarring to see this.”
Researchers are still trying to determine what went wrong. High Lp(a) may not actually cause heart attacks and strokes, but instead may be a marker for something else that increases risk.
Other possible explanations include timing. “Maybe you need to treat longer.
You may need to treat earlier, before people have advanced hardening of the arteries,” said Roger Blumenthal, a cardiologist at Johns Hopkins University.
Another possibility is that Lp(a)-lowering drugs may only help people with higher Lp(a) levels. “Maybe a higher Lp(a) should have been required for entry into the trial,” said David Maron, a Stanford University cardiologist who serves as president of the American Society for Preventive Cardiology.
Experts also said the study could have failed because Lp(a)-lowering drugs may only benefit people whose blood pressure and bad cholesterol were not as well controlled. Another explanation could be that pelacarsen itself does not produce a benefit, and other Lp(a)-lowering drugs might.
Several other drugmakers, including Amgen and Eli Lilly, are testing other experimental Lp(a)-lowering drugs, with results expected over the next few years. “The take-home message is the story’s not over,” said Karol Watson, a cardiologist at the University of California, Los Angeles.
“It’s kind of just starting.”
