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An experimental drug that doctors hoped would be the next big breakthrough in preventing heart attacks and strokes has failed a crucial test, researchers reported Saturday.
The drug, which reduces levels of a particle in the blood associated with heart attacks and strokes, did not protect volunteers in a closely monitored study.
“I was shocked. I had high hopes for success,” says Steven Nissencardiologist at the Cleveland Clinic who led the study. “Cardiovascular disease remains the leading cause of death in developed countries, so we were really hoping to find additional therapies that would reduce the risks.”
The research aimed to help people who seem to be doing everything right. They keep their cholesterol levels and blood pressure low, eat well, maintain a healthy weight, and exercise regularly. But many still suffer from heart attacks and strokes.
“These kinds of patients we see very frequently, and we were really doing our best to try to find a way to help these patients,” Nissen says.
Many of these patients have high blood levels of a cholesterol-carrying protein called lipoprotein(a) or Lp(a), which has long been thought to increase the risk of heart disease.
“About 20% of the world’s population has high levels. That’s about a billion people. So it’s a common disorder,” says Nissen.
Researchers search for drug to reduce Lp(a)
Until recently, doctors did not have a drug that could reduce Lp(a) levels. But several pharmaceutical companies have developed new experimental drugs in recent years that can significantly reduce high Lp(a) levels.
So, Nissen and colleagues gave 8,350 adults who already had heart disease either a placebo or a drug called pelacarsen, which reduces Lp(a).
The drug effectively suppressed Lp(a) levels by about 78%, the researchers showed. But after five years, this decline did not prevent people from suffering from cardiovascular complications.
“Very disappointing, terribly disappointing,” said Nissen, who presented the first details of the study at a conference American Heart Association Meeting in Chicago on Saturday and released more details in the New England Journal of Medicine and the NEJM proof.
Drugmaker Novartis, which sponsored the study, announced last month that the results of the study had not achieved their objectives, but without giving details.
In a statement, Novartis said the study “provides significant evidence” on the relationship between Lp(a) and heart disease and could “help inform future approaches to cardiovascular management.” “Scientific progress depends on pursuing difficult questions and studies (like the Pelacarsen study) play a crucial role in moving this field forward, even if the results are not what we had hoped for,” the company said.
What went wrong?
The failure of this drug to help patients is staggering, as many scientists, doctors and pharmaceutical companies hoped that Lp(a)-reducing drugs would be the next major weapon in the fight against cardiovascular disease, which kills more than 900,000 Americans each year.
“I think it’s a big deal because the expectations were so high that it would end up being positive,” says Harlan Krumholzcardiologist at Yale University. “And so it was really shocking to see that.”
Researchers wonder what went wrong.
It could be that high Lp(a) doesn’t actually cause a heart attack or stroke, but rather is a marker of something else that increases risk.
There could be other reasons why the study failed.
“Maybe you’ll need to treat for longer. You might need to treat sooner, before patients have advanced hardening of the arteries,” says Roger Blumenthalcardiologist at Johns Hopkins University.
Another possibility is that Lp(a)-lowering drugs might only help people with higher Lp(a) levels.
“Perhaps a higher Lp(a) should have been required to participate in the trial,” says David Maroncardiologist at Stanford University and president of the American Society for Preventive Cardiology.
The pelacarsen study may also have failed because Lp(a)-lowering drugs might only benefit people whose blood pressure and bad cholesterol were not as well controlled, several experts said.
Another explanation could be that there is something about pelacarsen, the experimental drug, that produces no benefit.
It is possible that other drugs that reduce Lp(a) do this.
Several other drugmakers, including Amgen and Eli Lilly, are testing other experimental Lp(a)-lowering drugs. The results of these trials should be available in the coming years.
“The take-home message is that the story is not over,” says Karol Watsoncardiologist at the University of California, Los Angeles. “It’s just getting started.”
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