The US Food and Drug Administration failed to adhere to its own internal guidance and practices during the approval process for Biogen’s Aduhelm Alzheimer’s drug, which was “fraught with irregularities,” a congress report showed on Thursday.
The FDA’s interactions with Biogen were “atypical” and did not follow the agency’s documentation protocol, according to a staff report on the findings of an 18-month investigation by two House committees on regulatory review, approval, price and marketing.
The FDA approved Aduhelm in June 2021 under an accelerated approval pathway despite objections from its panel of outside advisors, who did not believe the data definitively demonstrated the drug’s benefit to patients.
It was approved based on evidence that it could reduce brain plaques, a likely contributor to Alzheimer’s, rather than proof that it slowed the progression of the deadly, mind-wasting disease.
The Medicare program restricted its coverage, which has led to severely limited use of Biogen’s drug.
Biogen priced “unreasonably high” by initially pricing Aduhelm at $56,000 per year despite the lack of demonstrated clinical benefit in a broad patient population, the report said, adding that the company’s own internal projections they showed that he expected the drug to be a burden. for Medicare and expensive for patients.
“The findings of this report raise serious concerns about the FDA’s protocol flaws and Biogen’s disregard for efficacy and access in the Aduhelm approval process,” the report, prepared by the staff of the Committee on House Oversight and Reform and the House Power and Energy Committee. Trade, concluded.
The agency should ensure that all substantive interactions with drug sponsors are properly recorded, establish a protocol for joint briefing papers with drug sponsors, and update its industry guidance on new Alzheimer’s drug developments and reviews. , the report recommended.
Biogen and other drugmakers must communicate safety and efficacy concerns to the FDA, as well as take into account value and patient access when setting prices, according to the report.
An FDA spokesperson said the FDA’s decision to approve Aduhelm was based on a scientific evaluation of the data contained in the application.
He noted that the FDA’s internal review found its staff’s interactions with Biogen appropriate.
“It is the agency’s job to frequently engage with companies to ensure that we have the right information to inform our regulatory decision-making. We will continue to do so as it is in the best interest of patients,” she said, adding that the agency will continue to use the expedited approval pathway when appropriate.
The FDA has already begun implementing some of the report’s recommendations, the spokesperson said.
“Biogen stands by the integrity of the actions we have taken,” the Cambridge, Massachusetts-based biotech company said in an emailed statement.
“As stated in the congressional report, one (FDA) review concluded that, ‘There is no evidence that these pre-submission interactions with the sponsor were anything but appropriate in this situation,’” Biogen said.
Documents obtained by the committees show that FDA and Biogen staff conducted at least 115 meetings, calls, and email exchanges over a 12-month period beginning in July 2019.
The total number of meetings is unknown because the FDA did not keep a clear record of the informal meetings and interactions between its staff and Biogen representatives. The investigation identified an additional 66 calls and email exchanges that were not recorded.
The FDA inappropriately collaborated with Biogen on a joint briefing paper for the Central and Peripheral Nervous System (PCNS) Advisory Committee, according to the report, with FDA and Biogen staff working closely together for months prior to the meeting on November 6, 2020 to prepare the document. , which failed to adequately represent the different points of view within the agency.
“Using a joint briefing document enabled Biogen to learn the FDA’s responses and provide direct guidance from the agency in writing the company’s own sections. For example, in an exchange of the draft information document on October 9, 2020, FDA staff asked Biogen to move a paragraph redacted by the agency to the Biogen memo section, a change reflected when the document was finalized. document,” the report made public. to media organizations said.
When none of the advisory panel members voted to approve Aduhelm, the FDA switched to using its accelerated approval pathway, which is typically used for rare diseases or small populations of patients who lack access to effective treatments, despite having considered the drug under the traditional approval pathway for nine months, the report says.
It did so on a substantially shortened schedule, approving it after three weeks of review, and for a broad-label indication of “people with Alzheimer’s disease” that was not supported by clinical data, according to the report.
Internal documents obtained by the investigation showed that Biogen accepted the indication despite its own reservations about the lack of evidence that Aduhelm could help patients in stages of the disease outside of its clinical trials.