FDA requires investigation into controversial Alzheimer’s drug approval


TThe chief of the Food and Drug Administration has called for a full state investigation into the approval of Biogen’s treatment for Alzheimer’s disease just a month after a decision that sparked the ire of lawmakers, doctors, and public health advocates.

In a letter released on Friday, Acting Commissioner Janet Woodcock asked the independent office of the Inspector General to investigate how agency employees interacted with Biogen in advance of Aduhelm’s June 7 approval. The agency cited STAT’s report that FDA officials worked hand-in-hand with Biogen executives to bring the drug to market, including an unprecedented meeting and decision to approve Aduhelm by regulatory acronym.

“There remain concerns … about contacts between Biogen representatives and the FDA during the review process, including some that may have occurred outside of the formal correspondence process,” Woodcock wrote in a letter to acting Inspector General Christi Grimm. “To the extent that these concerns could undermine public confidence in the FDA’s decision, I believe it is crucial that the disputed events be reviewed by an independent body such as the Office of Inspector General to determine whether there is any difference between Biogen and the FDA’s investigators was not compliant with FDA guidelines and procedures. “


Woodcock added that she has “tremendous confidence in the integrity of the staff and leadership of the Center for Drug Evaluation and Research involved in the review of aducanumab and their commitment to impartial and science-based decision-making.”

STAT’s coverage has led to calls for an OIG investigation from stakeholders, former federal health officials and members of Congress.


Inspector General Investigations are among the most serious civil investigations that can be conducted against a federal agency. The Inspector General’s Office usually has extensive powers to subpoena internal FDA documents and conduct affidavits. The OIG can also refer potential criminal violations to the Department of Justice. However, no allegations of criminal behavior have been made against the FDA.

It is rare for the OIG to investigate the FDA, and even more exceptional for it to investigate a single drug approval decision, according to STAT’s review of public records. The Inspector General is currently reviewing a number of FDA programs, such as their systems for monitoring the safety of medical devices, although most of these requests are audits and evaluations, less serious forms of investigation.

“There should be an investigation, and it should be broad and not limited to the inadequate relationships between the FDA and Biogen,” said Gregg Gonsalves, professor at the Yale School of Public Health, who harshly criticized Aduhelm’s approval. “We need to know more precisely how the decisions were made within the agency because it was such a departure from normal procedures.”

Given the continued interest and questions, I asked @OIGatHHS today to conduct an independent review and assessment of the interactions between representatives from Biogen and the FDA during the process that led to Aduhelm’s approval. pic.twitter.com/iWJNxdZ5Cs

– Dr. Janet Woodcock (@DrWoodcockFDA) July 9, 2021

The OIG operates independently of federal agencies, and Woodcock’s letter does not guarantee that the Office will open an investigation. If OIG decides to investigate Aduhelm’s approval, it will eventually publish its findings in a public report.

In a statement, Biogen said it would cooperate with any federal investigation into Aduhelm’s approval.

Previous requests for an OIG investigation focused on the close relationship between Billy Dunn, the FDA’s chief neuroscience leader, and Biogen executives. Earlier this month, STAT reported that Biogen had a meeting with Dunn in May 2019 to seek his support for the treatment that would become Aduhelm. A month later, Dunn and his FDA colleagues suggested using an official abbreviation called expedited approval to approve the drug, contradicting the agency’s claim that it had only raised the option last March. The FDA was so supportive of Aduhelm that even in 2019 some within Biogen believed its approval was inevitable.

This week, two senior FDA officials told STAT that they were surprised the agency had decided to approve Aduhelm for all people with Alzheimer’s, rather than restricting it to those with milder forms of the disease who will be using the patients in clinical trials of the drug matched. One said they would not have supported the drug’s approval if they knew the FDA would give it such wide-ranging approval. Criticism of that decision led the agency to announce in a very unusual move on Thursday, so soon after approval, that it would drastically restrict the group of people Aduhelm is recommended for to those with the earliest stages of Alzheimer’s.

Biogen’s treatment, which aims to address the underlying cause of Alzheimer’s disease, has polarized scientists for years. The company conducted two large clinical studies to prove the benefits of Aduhelm. In one, the drug appeared to slow the progression of Alzheimer’s disease compared to placebo. In the other, Aduhelm failed, and the highest dose of treatment fared worse than saline.

As of 2019, the FDA worked closely with Biogen to argue that the overall data suggests that patients who receive high doses of Aduhelm for an extended period of time see measurable benefit on cognitive and functional tests. The resulting approval, based on objections from the FDA’s independent advisors, has sparked allegations of inappropriate behavior and regulatory overshoot.

“It would be really important to understand what happened and what kind of relationships might have influenced the decision,” said Steven Joffe, professor of medical ethics and health policy at the University of Pennsylvania’s Perelman School of Medicine. “It seems like an independent investigation that the OIG could conduct would be good for the public and stakeholders to understand the rationale behind the decision.”

A former FDA official said an investigation might actually help dissociate Woodcock from Aduhelm’s controversial decision. The longtime agency veteran is currently their acting commissioner, but she is one of the leading contenders for nomination for the full role. The official pointed out that while Woodcock was not involved in the approval decision, it was made by people raised in decision-making roles.

“Given the controversy surrounding the decision and all the irregular steps that have been taken, a review by the Inspector General’s Office is certainly warranted given all the irregularities related to previous decisions by the Agency,” said Joseph Ross. Professor of Medicine and Public Health at Yale. “I just hope that the research is done in time and that the results are published so that we can learn from it.”