The leader of the Food and Drug Administration on Friday called for a federal investigation into the agency's review and eventual approval last month of Biogen's Alzheimer's medicine Aduhelm, a serious and highly unusual step that follows immense controversy over the decision.
In a July 9 letter, Janet Woodcock, the FDA's acting commissioner, asked the Health and Human Services Inspector General to review interactions between Biogen executives and agency officials during the review process, and to determine whether those contacts violated FDA rules.
"There continue to be concerns raised," she wrote, "regarding contacts between representatives from Biogen and the FDA during the review process, including some that may have occurred outside of the formal correspondence process."
"To the extent these concerns could undermine the public's confidence in the FDA's decision, I believe that it is critical that the events at issue be reviewed by an independent body such as the Office of the Inspector General," she added. The HHS inspector general is an independent office of the health department, which houses the FDA, and has powers to subpoena and probe possible violations of law or policy.
The FDA approved Aduhelm on June 7 despite contradictory evidence from two clinical trials run by Biogen that left uncertain whether the drug actually helps improve the lives of people with Alzheimer's. Furthermore, the twin studies had originally failed, only for Biogen to claim success in one trial after reviewing additional data.
The nearly year-long review process was unorthodox, featuring substantial collaboration between the agency and the Cambridge, Massachusetts-based biotech company. Last November, at a meeting of outside experts convened by the FDA, officials from the regulator appeared to advocate in favor of the drug, even presenting their views in a joint document together with Biogen's. The advisory committee overwhelmingly voted against the drug.
A recently published investigation by STAT News found a top FDA official met with Biogen's chief medical officer in May 2019, before the drug was submitted for approval, raising questions about a possible "back channel" of influence. STAT first reported Woodcock's call for an investigation Friday.
"We will, of course, cooperate with any inquiry in connection with a possible review of the regulatory process," a Biogen spokesperson wrote in an email to BioPharma Dive.
In her letter, Woodcock personally committed to cooperate with an investigation, should the HHS inspector general choose to begin one.
The long-time official noted, however, her "tremendous confidence" in the staff of the FDA office involved in the review and their commitment to "unbiased and science-based decision-making."
Their decision-making has been called into question, however, particularly as documents disclosed by the FDA have more fully detailed the disagreement between agency statisticians and the other teams involved in Aduhelm's review. The statisticians argued Biogen's evidence did not merit approval, but were overruled by the other offices, all of which supported clearing the drug.
Additionally, the documents shed light on what appears to have been a consequential April 26 meeting between high-ranking FDA leaders, including Patrizia Cavazzoni, the head of the agency's main drug review office and reportedly a close ally of Woodcock.
At the meeting, the assembled officials concurred with the review team's support for Aduhelm, seemingly cementing the subsequent approval.
Adding to the controversy, the FDA initially chose to clear Aduhelm for all Alzheimer's patients, despite Biogen having never tested the drug in patients with moderate to more severe disease. Earlier this week, the agency took the unusual step of walking that recommendation back, instructing doctors to limit treatment to only those with mild dementia.
Criticism has come from many sides in the month since Aduhelm's approval. Three members of the advisory committee consulted by the FDA in November have resigned in protest, with one calling the OK "probably the worst drug approval decision in recent U.S. history."
Public Citizen, an outspoken advocacy group, has called for the resignation of several top officials, including Woodcock and Cavazzoni. On Friday, the group urged the inspector general to keep a review broad, examining Woodcock's role as well.
Several lawmakers, including powerful Senate Finance chair Ron Wyden, D-Ore., have also expressed concern over the approval. More recently, Democratic congresswoman Katie Porter, of California, asked for an investigation of the FDA's contacts with pharmaceutical companies, citing Aduhelm's approval.
Their objections have also centered on the drug's price, which Biogen set at an average cost of $56,000 per year. Experts predict use of the drug could add tens of billions of dollars to Medicare's budget for doctor-administered drugs.
The pressure appears to have reached FDA officials, including Woodcock, who have strongly defended the approval in news interviews and other appearances.
Aduhelm is the first drug approved for Alzheimer's in nearly 20 years and the first ever to treat what many experts have argued is the disease's underlying cause. Biogen, which licensed the compound that became Aduhelm from Swiss biotech Neurimmune, spent more than a decade and over $1 billion dollars developing the drug together with Japan's Eisai.
In approving Aduhelm, the FDA chose to clear the drug on a conditional basis, citing the uncertainty of the trial data but also the likelihood that the drug's effects on a brain plaque associated with Alzheimer's were predictive of a benefit.
By doing so, the agency embraced a much-debated hypothesis for treating the memory-robbing disease and set a precedent that other drugmakers are already looking to follow. Eli Lilly recently said it would ask the FDA for accelerated approval of an experimental medicine that works similarly to Aduhelm, and Roche is reportedly considering the same with one of its own drugs.
Ben Fidler contributed reporting.