The Food and Drug Administration on Thursday limited the recommended use of a controversial new Alzheimer’s drug to patients with mild cognitive impairment or early dementia from the disease—a major change from the original label that included everyone with the illness.
The revised label clarifies that the drug, called Aduhelm, is intended for patients with early-stage disease—the population that participated in clinical trials of the drug, according to statements from the FDA and Biogen, the drug’s manufacturer. The drug was approved June 7—the first Alzheimer’s medication cleared since 2003—sparking heated debates about whether it slows cognitive decline, as it was intended to do.
The narrower label means the drug might be offered to 1 million or 2 million Alzheimer’s patients, rather than the more than 6 million people with Alzheimer’s in the United States, Michael Yee, a biotech analyst for the financial services company Jefferies, said in a note to investors.
Yee said the original label led to “negative attention and confusion on who is best suited to get the drug” and raised questions about whether Medicare and private insurers would reimburse for the medication, which has a list price of $56,000 a patient per year.
Some doctors had expressed concern that they would face pressure from desperate families to offer the drug to later-stage patients even though it was not tested on them. Many said they would consider providing it only to earlier-stage patients.
The FDA granted the drug “accelerated approval” based on its effectiveness at removing amyloid plaque from the brain, which the agency said offered a reasonable likelihood that patients could benefit. The agency directed Biogen to verify a benefit to patients in a confirmatory study due in nine years.
The FDA said Thursday in a statement that “it was important to clarify the intent” of the label—specifically, that any initiation of Aduhelm should occur in patients in the mild cognitive impairment or early dementia stages of Alzheimer’s. The agency said that information was included in one section of the label but that it wanted to give it more prominence. The FDA added that “some patients may benefit from ongoing treatment” even if they progress to later stages.
But in a news briefing earlier this month, after the drug was approved, Peter Stein, director of the FDA’s Office of New Drugs, said: “It’s not expected that this would only be relevant necessarily in early stages because amyloid is a key part, is a hallmark of the disease through its entire course. The expectation is that this drug will provide benefit across that spectrum.”
Alfred Sandrock Jr., Biogen’s head of research and development, said in a statement Thursday that Biogen, after talking to the FDA, physicians and patient advocates, had submitted revised prescribing information “with the goal to further clarify the patient population” for whom the drug would be appropriate. Biogen said there are no safety or effectiveness data for starting the drug in groups of patients who were not studied. Those include people who are pre-symptomatic or have advanced disease.
The original label is just one of many controversies surrounding the medication. Critics argue that clinical trials of the drug did not provide proof of effectiveness and that the drug should not have been approved. An advisory committee recommended against clearance. Members of Congress have said they will hold hearings on the issue.
Aaron Kesselheim, a Harvard Medical School professor who was one of three experts who quit the advisory board after the FDA approved the drug, said on Twitter that he welcomed the label change but that the FDA and Biogen “should be doing much more now to help patients by actively combatting misperceptions about this drug.”