Initial approval of Aduhelm in June broadly stated the drug was “indicated for the treatment of Alzheimer’s disease,” leaving open the possibility that the $56,000 a year medicine could be sought by and prescribed to the estimated 5.8 million Americans who have the neurodegenerative disorder. In updating the label to say the drug should be given to patients with “mild cognitive impairment or mild dementia,” the regulator brings the indicated use of the drug in alignment with the patient population that was studied in clinical trials.
The updated information further states that “there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.”
Once a drug is approved, physicians may prescribe it as they see fit—regardless of the drug label. But following the outcry to response to the broad language in Aduhelm’s label, Cambridge, Massachusetts-based Biogen in late June issued a statement emphasizing that the drug had only been tested in patients in the early stages of Alzheimer’s disease, and that the company’s outreach to medical professionals would focus on that patient population, which the company estimates is between 1 million and 2 million people.
The drug label update was requested by Biogen. In a prepared statement, Alfred Sandrock, Biogen’s head of research and development, said the label change was based on the company’s conversations with physicians, the FDA, and patient advocates. It’s a change that comes as the company and the agency face mounting questions about the efficacy of Aduhelm and the regulatory process used to approve it. Even supporters of the drug have criticized the product’s annual price tag, much of which will be shouldered by Medicare.
Aduhelm is an antibody drug designed to break up the plaques of amyloid protein that build up on the brain. While the buildup of this protein is characteristic of Alzheimer’s disease, it’s unknown whether clearing away amyloid plaque will improve the symptoms of the disease. The main goal of the Phase 3 clinical trials was to show a slowing in cognitive decline.
Two Phase 3 tests of Aduhelm were stopped in 2019 after an independent analysis found that they were unlikely to achieve the main study goal. But Biogen conducted another analysis of a larger dataset. Based on that new analysis, Biogen said that one of the two Phase 3 tests succeeded. Those data were the basis of the application seeking regulatory approval.
An independent panel of medical experts that advises the FDA on drug decisions voted against recommending approval of Aduhelm. The FDA ended up approving the drug under the agency’s accelerated approval pathway, which is speedier than a standard review and is based on less evidence. Approvals under this pathway can be based on a “surrogate endpoint,” a sign in clinical trials that a drug might be working even if the data do not definitively show patient benefit. The FDA approved Aduhelm on the surrogate endpoint of clearance of amyloid plaque in patients.
Confirmation of Aduhelm’s benefit must come from additional clinical research conducted after a drug reaches the market. The confirmatory study for Aduhelm could take up to nine years. Congressional hearings could come sooner. On June 25, Democratic leaders of two House committees announced that they would examine the approval and pricing of Aduhelm despite concerns about its benefit to patients.
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