TThe head of the Food and Drug Administration has called for a comprehensive federal investigation into the approval of Biogen’s treatment for Alzheimer’s disease just one month after a decision sparked outrage among lawmakers, doctors and public health advocates.
In a letter published Friday, Acting Commissioner Janet Woodcock asked the Independent Inspector General’s Independent Office to investigate how the agency’s staff interacted with Biogen in the June 7 approval of Aduhelm. The agency cited STAT’s report that FDA officials worked hand in hand with Biogen executives to get the drug on the market, including an off-the-books meeting and an unprecedented decision to approve Aduhelm through a legislative shortcut.
“Concerns remain … regarding contacts between Biogen and FDA representatives during the review process, including some that may have taken place outside the formal correspondence process,”
Woodcock added that she has “tremendous confidence in the integrity of the staff and management of the Center for Drug Evaluation and Research involved in the aducanumab review and their commitment to impartial and science-based decision-making.”
STAT’s reporting has prompted calls for an OIG inquiry from advocacy groups, former federal health officials and members of Congress.
General inspectors are among the most serious types of civil investigations that can be conducted in a federal agency. The inspector’s office typically has broad authority to convene internal FDA documents and to conduct interviews under oath. The OIG may also refer potential criminal offenses to the Department of Justice. However, no allegations of criminal conduct have been made against the FDA.
It is rare for the OIG to investigate the FDA, and even more unusual for it to examine an individual drug approval decision according to STAT’s review of public records. The Inspector General is currently reviewing a number of FDA programs, as well as its systems for monitoring the safety of medical devices, although the majority of these investigations are audits and evaluations, less serious types of investigations.
“There should be a study, and it should be broad-based and not limited in scope to the incorrect relationship between the FDA and Biogen,” said Gregg Gonsalves, a professor at the Yale School of Public Health who has been sharply critical of Aduhelm’s approval. . “We need to know in more detail how the decision-making was done within the agency because it was such a departure from the normal procedure.”
Given the ongoing interest and questions, I requested today that @OIGatHHS conduct an independent review and assessment of interactions between representatives of Biogen and the FDA during the process leading to the approval of Aduhelm. pic.twitter.com/iWJNxdZ5Cs
– Dr. Janet Woodcock (@DrWoodcockFDA) July 9, 2021
The OIG operates independently of any federal agency, and Woodcock’s letter does not guarantee that the office will initiate an investigation. If the OIG chooses to examine the Aduhelm approval, it will eventually publish its findings in a public report.
Previous calls for an OIG study have focused on the close relationship between Billy Dunn, head of the FDA’s neuroscience department, and Biogen executives. Earlier this month, STAT reported that Biogen had an off-the-books meeting with Dunn in May 2019, where he supported the treatment that would become Aduhelm. One month later, Dunn and his FDA colleagues proposed using a legislative shortcut called accelerated authorization to get the drug approved, which contradicts the agency’s claim that it only raised this possibility in March. The FDA was so supportive of Aduhelm that even in 2019, some within Biogen believed that its approval was inevitable.
This week, two senior FDA officials told STAT that they were surprised that the agency chose to approve Aduhelm for all people with Alzheimer’s disease rather than restricting it to those who matched the patients in the drug’s clinical trials. One said they would not have supported the approval of the drug if they knew the FDA would grant it such an expansive approval.
Biogen treatment, designed to tackle the underlying cause of Alzheimer’s, has polarized researchers for years. The company ran two large clinical trials to prove Aduhelm’s benefits. In one, the drug appeared to slow the progression of Alzheimer’s versus placebo. In the second, Aduhelm failed, and the highest dose of treatment performed worse than a saline solution.
As of 2019, the FDA worked closely with Biogen to highlight that the data overall suggest that patients receiving a high dose of Aduhelm for extended periods of time see a measurable benefit in testing for cognition and function. The resulting approval, which came across the objections of the FDA’s independent advisers, has given rise to allegations of misconduct and regulatory overruns.
“It would be very important to understand what was going on and what kind of conditions could have influenced the decision,” said Steven Joffe, professor of medical ethics and health policy at the Perelman School of Medicine. “It seems that an independent study that OIG could do would be good for the public and stakeholders to understand the background behind the decision.”
A former FDA official said an investigation could actually help remove Woodcock from the controversial Aduhelm decision. The longtime agency veteran is currently its acting commissioner, but she is a leading candidate to be nominated for the full role. The official pointed out that although Woodcock was not involved in the approval decision, it was made by people she had raised to decision-making roles.
“Given the controversy surrounding the decision and all the irregular steps that have been taken, a review of the Inspector’s Office is certainly justified given all the irregularities in previous decisions taken by the Agency,” said Joseph Ross, Professor of Medicine and Public Health at Yale. “I just hope the investigation will happen in a timely manner and the results will be published so we can learn from them.”
Matthew Herper and Nicholas Florko contributed reporting.