Mass General Brigham is unlikely to offer Biogen’s controversial new Alzheimer’s drug to patients taking blood thinners because of concerns about the risk of bleeding in the brain, according to two doctors helping to develop a policy on the medicine for the state’s largest health care provider.
Dr. Teresa Gomez-Isla and Dr. Kirk Daffner, Alzheimer’s specialists at Massachusetts General Hospital and Brigham and Women’s Hospital, respectively, noted that patients on anticoagulant medications were excluded from clinical trials of the recently approved Aduhelm. The Cambridge biotech’s medicine was associated with “microhemorrhages,” or small amounts of bleeding, in the brains of some patients in the studies but usually didn’t cause serious problems.
Although the Food and Drug Administration narrowed its previous recommendations for using Aduhelm last Thursday, the revised guidelines don’t mention that it wasn’t tested on patients taking blood thinners. That omission has alarmed some prominent US doctors who say such patients could be at risk for worse bleeding.
At least 8 million Americans take blood thinners, according to the nonprofit National Blood Clot Alliance, making it one of the most commonly prescribed classes of drugs. Anticoagulants keep blood flowing smoothly in veins and arteries, and physicians often recommend them to patients at risk for heart attacks and strokes.
More than a third of patients who took Aduhelm in clinical trials had small brain bleeds or an accumulation of fluid detected by MRI. The problem generally went away on its own, but some participants reported confusion or dizziness.
“There is a legitimate concern that anticoagulant medication (blood thinners) could transform microhemorrhages . . . into clinically worrisome cerebral bleeds,” Daffner, Brigham’s chief of cognitive and behavioral neurology, said in an e-mail.
Given that researchers didn’t study whether Aduhelm can cause serious bleeding for patients on blood thinners, “it is prudent” not to prescribe the drug to them, Daffner wrote. He said that Mass General Brigham ”and many other centers are likely to adopt a policy of not including patients on anticoagulants.”
Ultimately, a panel of medication experts at Mass General Brigham will vote on whether the health care system should prescribe Aduhelm, as it does with all approved drugs, said Gomez-Isla, who oversees the memory division at Massachusetts General Hospital’s department of neurology. She, Daffner and other doctors will advise the panel before the vote, which is expected in the fall.
Still, Gomez-Isla said in an e-mail that she “would be reluctant to recommend this treatment” to patients on blood thinners “at this time based on a concern from a safety standpoint. Given the lack of data on those patients, it is unclear whether they would be helped or in fact harmed.”
Mass. General and Brigham and Women’s both participated in clinical trials of Aduhelm. Daffner and Gomez-Isla said last week that they considered the FDA approval “premature” and would have preferred Biogen conduct a third late-stage clinical trial.
A Biogen spokeswoman, Allison Parks, on Thursday confirmed that people on prescription blood thinners were excluded from clinical trials to avoid “exposing patients to unnecessary risks.” Patients who take less than 325 milligrams of aspirin a day to help prevent blood clots were allowed to participate.
As a result, she said, “we don’t have robust data to fully clarify any potential” drug interactions. “Biogen supports physicians as they make personalized decisions regarding treatment based on their patients’ needs while balancing safety and efficacy,” she said.
The FDA did not immediately respond to requests for comment.
The emerging position of Mass General Brigham, one of the most respected medical systems in the country, represents the latest fallout from the FDA’s approval of Aduhelm on June 7. The agency’s ruling has spurred investigations by Congress and the Department of Health and Human Services’ independent Office of the Inspector General.
The approval has also drawn fire from medical experts and some health insurance companies, some of whom are balking at Aduhelm’s annual average price tag of $56,000 per patient.
On Wednesday evening, two other renowned health systems, the Mount Sinai Health System in New York and the Cleveland Clinic, said they will not administer Aduhelm to patients, following a review of scientific evidence and related matters. No hospital system in Massachusetts has announced such a firm stand.
Dr. Sam Gandy, director of the Mount Sinai Center for Cognitive Health, said his hospital’s decision was driven by several factors, one of which is that the FDA process for approving the drug is under investigation by an inspector general for the Department of Health and Human Services.
Acting FDA Commissioner Dr. Janet Woodcock requested the investigation last Friday, citing interactions between Biogen representatives and drug regulators, first reported by the news site STAT, that “may have occurred outside of the formal correspondence process.”
Gandy said in an interview that despite the FDA announcement last week that Aduhelm should be prescribed to people with mild memory or thinking problems ― a dramatic narrowing of the agency’s initial guidelines ― the recommendations are still “laughably broad.”
The fact that people on blood thinners were barred from participating in the trials but can be prescribed the approved drug, Gandy said, is a prime example of the lax guidelines for use. Among the drugs doctors commonly prescribe to prevent blood clots are heparin, coumadin, and clopidogrel, he said, sometimes in a combination.
Gandy was puzzled by another discrepancy between the trials and FDA guidelines for the drug. Patients who received Aduhelm in clinical trials were barred from further participation if imaging tests revealed they had suffered 10 microhemorrhages, he said. But the revised guidelines say patients prescribed Aduhelm can have 10 or more microhemorrhages and stay on the drug as long as brain imaging tests indicate “stabilization” without defining what that means, he said.
Biogen had no comment on the discrepancy, said Parks.
Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California, who also worked on one of the clinical trials of Aduhelm and opposed its approval, said he, too, was baffled by the omission of anticoagulants in the FDA guidelines.
“Blood thinners are one of the most commonly prescribed drugs for elderly people,” he said.
Aduhelm is a monoclonal antibody made from the immune cells of older people with no or uncommonly slow cognitive decline. It is administered in monthly intravenous infusions and has raised the hopes of many families affected by Alzheimer’s, their advocates, and some physicians.
The drug generated conflicting results in two late-stage clinical trials. In one study, Biogen said, a high dose could delay cognitive decline by 22 percent, an encouraging result. The other trial failed to prove the drug was effective.
Aduhelm is the first new drug for Alzheimer’s approved since 2003 and is expected to be a blockbuster. The FDA cleared it under an “accelerated approval pathway” reserved for medicines that fill a serious unmet need.
Jonathan Saltzman can be reached at firstname.lastname@example.org.