US regulator broke own protocols in approving Alzheimer’s drug

The US Food and Drug Administration (FDA) failed to adhere to its own guidance and internal practices during the approval process for Biogen’s Alzheimer’s drug Aduhelm, which was “rife with irregularities,” a congressional report says.

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 government committees into the drug’s regulatory review, approval, pricing, and marketing.

The FDA approved Aduhelm in June 2021 under an accelerated approval pathway over the objections of its panel of outside advisers, who did not believe data definitively proved the drug’s benefit to patients. It was authorised 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 health insurance programme restricted its coverage, which has led to severely limited use of the Biogen drug.

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Biogen set an “unjustifiably high” price by initially setting Aduhelm’s price at $56,000 (€52,679) a 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 house of representative’s committee on oversight and reform and committee on energy and commerce, concluded.

The agency should ensure that all substantive interactions with drug sponsors are properly memorialised, 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 spokesman said its 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.

The FDA has already begun implementing some of the report’s recommendations, the spokesman said.

“Biogen stands by the integrity of the actions we have taken,” the 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 July 2019. 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 memorialised.

The FDA inappropriately collaborated with Biogen on a joint briefing document for the peripheral and central nervous system advisory committee, the report said, with FDA and Biogen staff working closely for months in advance of the November 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,” the report made public to media organisations 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, approving it 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. – Reuters