The U.S. Food and Drug Administration failed to adhere to its own guidance and internal practices during the approval process for the Biogen Alzheimer’s drug Aduhelm, a new report states.
That process was “rife with irregularities,” a congressional report showed this week.
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 conducted by two House committees into the drug’s regulatory review, approval, pricing and marketing.
The FDA approved Aduhelm, the brand name for the drug aducanumab, in June 2021 under an accelerated approval pathway over the objections of its panel of outside advisers, who did not believe the data definitively proved the drug’s benefit to patients.
It was authorized based on evidence that it could reduce brain plaques, a likely contributor to Alzheimer’s, rather than proof that it slowed progression of the lethal mind-wasting disease.
The Medicare program restricted its coverage, which has led to severely limited use of the drug.
Biogen set an “unjustifiably high” price by initially setting Aduhelm’s price at $56,000 per year despite a lack of demonstrated clinical benefit in a broad patient population, the report said, adding that the company’s own internal projections showed it expected the drug to be a burden to Medicare and costly to patients.
“The findings in this report raise serious concerns about FDA’s lapses in protocol and Biogen’s disregard of efficacy and access in the approval process for Aduhelm,” the report, prepared by the staffs of the House Committee on Oversight and Reform and House Committee on Energy and Commerce, concluded.
The agency should ensure that all substantive interactions with drug sponsors are properly memorialized, establish a protocol for joint briefing documents with drug sponsors, and update its industry guidance on the developments and review of new Alzheimer’s drugs, the report recommended.
Biogen and other drugmakers should communicate to the FDA any concerns over safety and efficacy as well as take value and patient access into consideration when setting prices, the report said.
An FDA spokesperson said the agency’s decision to approve Aduhelm was based on scientific evaluation of the data contained in the application.
He pointed to the FDA’s internal review finding its staff’s interactions with Biogen appropriate.
“It is the agency’s job to frequently interact with companies in order to ensure that we have adequate information to inform our regulatory decision-making. We will continue to do so, as it is in the best interest of patients,” he said, adding that the agency will continue to use the accelerated approval pathway whenever appropriate.
The FDA already has begun implementing some of the report’s recommendations, the spokesperson said.
Biogen once had a major presence in San Diego (after its 2003 merger with San Diego’s Idec Pharmaceuticals), but closed its Nobel Campus in the University Towne Center area in 2010.
“Biogen stands by the integrity of the actions we have taken,” the Cambridge, Mass.-based biotech company said in an emailed statement.
“As stated in the congressional report, an (FDA) review concluded that, ‘There is no evidence that these interactions with the sponsor in advance of filing were anything but appropriate in this situation,’” Biogen said.
Documents obtained by the committees show that FDA staff and Biogen held at least 115 meetings, calls and email exchanges over a 12-month period starting in July 2019.
In December of that year, Biogen discussed results at the 12th Clinical Trials on Alzheimer’s Disease conference at the Hilton San Diego Bayfront.
The total number of meetings is unknown because the FDA failed to keep a clear record of informal meetings and interactions between its staff and Biogen representatives. The investigation identified an additional 66 calls and email exchanges that were not memorialized.
The FDA inappropriately collaborated with Biogen on a joint briefing document for the Peripheral and Central Nervous System (PCNS) Advisory Committee, the report said, with FDA and Biogen staff working closely for months ahead of the Nov. 6, 2020 meeting to prepare the document, which failed to adequately represent differing views within the agency.
“Using a joint briefing document afforded Biogen advance insight into FDA’s responses and direct guidance from the agency in drafting the company’s own sections. For example, in an exchange of the draft briefing document on Oct. 9, 2020, FDA staff asked Biogen to move a paragraph drafted by the agency into Biogen’s section of the memorandum – a change reflected when the document was finalized,” the report made public to media organizations said.
When none of the advisory panel members voted to approve Aduhelm, the FDA pivoted to using its accelerated approval pathway – typically used for rare diseases or small patient populations that lack access to effective treatments – despite having considered the drug under the traditional approval pathway for nine months, the report said.
It did so on a substantially abbreviated timeline, with approval coming after three weeks of review, and for a broad label indication of “people with Alzheimer’s disease” that was unsupported by clinical data, the report said.
Internal documents obtained by the investigation showed that Biogen accepted the indication despite its own reservations over the lack of evidence Aduhelm could help patients at disease stages outside of its clinical trials.
(Reporting by Ahmed Aboulenein, editing by Diane Craft)