Amgen and Sanofi sponsored studies identify new class of drugs known to lower cholesterol and reduce risk of heart attacks
Monday, March 16, 2015
Studies are likely to fuel increased interest in the new drug class.
Researchers reported the first evidence that a new class of drugs known to dramatically lower cholesterol may also reduce risk of heart attacks, strokes and other serious consequences of cardiovascular disease.
The reports, from relatively small studies sponsored by Amgen Inc. and by Sanofi SA and its partner Regeneron Pharmaceuticals Inc., found that the drugs cut risk of major cardiovascular events by about half.
While not definitive, the results are likely to fuel already intense interest in the agents, known as PCSK9 inhibitors. Amgen and Sanofi-Regeneron are neck-and-neck in a race to bring the agents to market. The U.S. Food and Drug Administration is expected to decide whether to approve their drugs by this summer. Pfizer Inc. is also in the hunt with a third candidate.
The blockbuster class of drugs called statins is the mainstay medicine against LDL cholesterol. Statins, best known by popular Pfizer Inc. drug Lipitor, are among the most widely prescribed and most lucrative products ever developed by the pharmaceutical industry. But millions of patients, for genetic reasons, for instance, or because of side effects, aren’t able to get their LDL under control with statins. The PCSK9 inhibitors block a protein that interferes with the liver’s ability to clear LDL and are viewed as an important potential option for such patients.
Studies involving all three drugs over the past few years have shown that they cause profound drops in LDL or bad cholesterol, which at elevated levels is a key risk factor for heart attacks and strokes.
But yet to be shown is whether the much lower LDL translates into a lower risk of serious consequences of cardiovascular disease.
The new studies evaluated only a small number of events with a short follow-up and had other important limitations that called for caution in interpreting the results, researchers said. They may have overestimated the benefits and underestimated side effects. All three companies are doing much larger, more rigorous studies to look at the long-term effects of the medicines, but results aren’t likely until 2017 or 2018.
“While you’re awaiting those data,” said Marc S. Sabatine, a cardiologist and chairman of the TIMI Study Group at Brigham and Women’s Hospital, Boston, the new studies provide “some early clinical outcomes data that is reassuring.”
Dr. Sabatine is lead author of the study of Amgen’s drug evolocumab. He presented the findings Sunday at the annual meeting of the American College of Cardiology. The results were also published, along with the Sanofi-Regeneron study, online by the New England Journal of Medicine.
The Amgen study enrolled 4,465 participants from previous smaller evolocumab studies and re-randomized them to either the drug or placebo. After nearly a year of follow-up, just under 1% of those assigned to evolocumab had suffered a major heart-related event, compared with just over 2% of those on placebo.
Side effects were generally similar among the two groups but adverse cognitive events, though rare, measured 0.9% on the drug and 0.3% on placebo, Dr. Sabatine reported. They included reports of confusion, attention deficits and mental impairment.
Judith Hochman, director of cardiovascular clinical research at New York University Langone Medical Center, called the overall findings “really impressive and very encouraging for this class of cholesterol agents.”
For Sanofi-Regeneron’s drug alirocumab, researchers led by Jennifer Robison of the University of Iowa Carver College of Medicine described similar results in the New England Journal. The study of 2,341 patients followed for 78 weeks reported major heart-related events in 1.7% of patients on the medicine vs. 3.5% on placebo and cognitive side effects for 1.2% of alirocumab patients and 0.5% for those on placebo.
The FDA has already taken note of reports of cognitive side effects; at the agency’s request, all three companies said they are evaluating the issue in the ongoing major trials.
Anthony DeMaria, a cardiologist at University of California, San Diego and a past ACC president, termed the results of the studies “encouraging” and said he would prescribe the drugs now, if they were available, for high-risk patients unable to take statins. But for use in a wider population, he said he’d want first to see the efficacy and side-effect data from the definitive trials.
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