What happens when a regulator is too close to the regulated
The Food and Drug Administration’s process for scrutinizing new drugs is unrivaled in the world, and the American people expect it to demand a high standard for safety and efficacy. But a congressional oversight staff report released Dec. 29 on the application of Biogen for its Alzheimer’s drug, Aduhelm, highlights serious lapses by the company and agency. Their cozy dealing undermines public trust.
Alzheimer’s disease afflicts more than 6 million Americans, and the devastating loss of cognitive ability is a tragedy to victims and their loved ones. For nearly two decades, the public has hoped in vain for an effective medicine to fight it. “Our ambition is to make history,” declared a Biogen board presentation in September 2020, according to the report of an 18month long investigation in the last Congress by the House Oversight and Reform Committee under Chairwoman Carolyn B. Maloney, D.-N.Y., and Energy and Commerce Chairman Frank Pallone Jr., D.-N.J.
Biogen began two clinical trials on Aduhlem in 2015 but discontinued them in 2019 when it appeared the trials would not meet their goals. But then Biogen claimed further analysis of the data could demonstrate some clinical benefit. The company and the FDA proceeded to work together on a new drug application to the agency. The congressional report says they engaged in at least 115 meetings, calls and substantive email exchanges, although the precise total is not known because records were not properly kept. The FDA has collaborated with applicants in the past, but its own internal review found this case “exceeded the norm in some respects” and Biogen internal documents mentioned a “high-touch engagement strategy with regulators.” High-touch indeed: A presentation to an FDA advisory committee about Aduhelm was written jointly by Biogen and the FDA.
When the FDA decided to move Aduhelm to an accelerated approval pathway, it did not consult any external advisory body or internal expert group, which the congressional report calls “a particularly notable lapse.” FDA officials have defended this pivot to accelerated approval, saying it was consistent with the law, but in retrospect it seems hasty. When the FDA approved Aduhelm in June 2021, it was with a label indicating it would be used to treat “people with Alzheimer’s disease,” even though the clinical trial population was far narrower. Biogen knew the broad label would cause confusion, but the company did not object and accepted the broad label, which had to be revised later.
The FDA says it is acting on recommendations of its internal review. Commissioner Robert M. Califf said “nobody’s in trouble” as a result but admitted the agency erred by failing to properly document its interactions with the drug company. Biogen says it “stands by the integrity of the actions” has taken. Judging by this staff report, both the FDA and Biogen put their credibility at risk. The FDA should accept no shortcuts or substitutes to ensuring its processes are scientifically sound and unassailably independent.