In a letter posted Friday, acting Commissioner Janet Woodcock asked the independent Office of Inspector General to investigate how agency staff interacted with Biogen in the run-up to the June 7 approval of Aduhelm. The agency cited STAT’s reporting 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 regulatory shortcut.
“There continue to be concerns raised … regarding contacts between representatives from Biogen and 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 these concerns could undermine the public’s confidence in FDA’s decision, I believe it is critical that the events at issue be reviewed by an independent body such as the Office of Inspector General in order to determine whether any interactions that occurred between Biogen and FDA review staff were inconsistent with FDA policies 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 aducanumab review and their commitment to unbiased and science-based decision-making.”
STAT’s reporting has prompted calls for an OIG investigation from advocacy groups, former federal health officials, and members of Congress.
Inspector general investigations are among the most serious types of civil investigations that can be conducted into a federal agency. The inspector general’s office typically has broad power to subpoena internal FDA documents and to conduct interviews under oath. The OIG can also refer potential criminal violations 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 exceptional for it to investigate an individual drug approval decision, according to STAT’s review of public records. The inspector general is currently reviewing a number of FDA programs, like its systems for monitoring the safety of medical devices, though the majority of those inquiries are audits and evaluations, less serious forms of investigations.
“There should be an investigation, and it should be broad-based and not limited in scope to the improper relationships between the FDA and Biogen,” said Gregg Gonsalves, a professor at Yale School of Public Health who has been sharply critical of Aduhelm’s approval. “We need to know in greater detail about how the decision-making was done within the agency, because it was such a departure from normal procedure.”
The OIG operates independently from any federal agency, and Woodcock’s letter does not guarantee the office will mount an investigation. If OIG chooses to investigate the Aduhelm approval, it will eventually publish its findings in a public report.
In a statement, Biogen said it would cooperate with any federal inquiry into the approval of Aduhelm.
Earlier calls for an OIG investigation have focused on the close relationship between Billy Dunn, head of the FDA’s neuroscience division, and Biogen executives. Earlier this month, STAT reported that Biogen had an off-the-books meeting with Dunn in May 2019, enlisting his support for the treatment that would become Aduhelm. A month later, Dunn and his FDA colleagues proposed using a regulatory shortcut called accelerated approval to get the drug approved, contradicting the agency’s claim that it raised that option only this past March. The FDA was so supportive of Aduhelm that, even in 2019, some inside Biogen believed its approval was inevitable.
This week, two senior FDA officials told STAT they were surprised the agency chose to approve Aduhelm for all people with Alzheimer’s, rather than restricting it to those with milder forms of the disease who matched the patients in the drug’s clinical trials. One said they would not have supported approving the drug had they known the FDA would give it such an expansive approval. Criticism of that decision led the agency to announce on Thursday, in a highly unusual move so soon after approval, that it would dramatically narrow the group of people for whom Aduhelm is recommended, to those with the earliest stages of Alzheimer’s.
Biogen’s treatment, meant to address the underlying cause of Alzheimer’s, has polarized scientists 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 other, Aduhelm failed, and the highest dose of the treatment fared worse than a saline solution.
Starting in 2019, the FDA worked closely with Biogen to make the case that, when taken as a whole, the data suggest patients who get a high dose of Aduhelm for an extended period of time see a measurable benefit on tests of cognition and function. The resulting approval, which came over the objections of the FDA’s independent advisers, has seeded allegations of improper conduct and regulatory overreach.
“It would be really important to understand what went on and what sort of relationships might have influenced the decision,” said Steven Joffe, professor of medical ethics and health policy at the University of Pennsylvania Perelman School of Medicine. “It seems like an independent investigation, which the OIG could do, would be good for the public and stakeholders to understand the background behind the decision.”
One former FDA official said that an investigation could actually help distance Woodcock from the controversial Aduhelm decision. The longtime agency veteran is currently its acting commissioner, but she is a leading contender to be nominated for the full role. The official pointed out that even though Woodcock was not involved in the approval decision, it was made by people she had elevated to decision-making roles.
“Given the controversy surrounding the decision and all the irregular steps that were taken, a review by the Office of the Inspector General is certainly warranted, given all of the irregularities in the context of past decisions made by the agency,” said Joseph Ross, a professor of medicine and public health at Yale. “I just hope the investigation will happen in a timely way and the findings will be made public so we can learn from them.”