Two powerful congressional committees investigating the controversial federal approval of Biogen’s Alzheimer’s drug, Aduhelm, demanded extensive information and documents from the Food and Drug Administration in a letter released on Thursday, making it clear that the committees’ leaders are troubled by unusual actions the agency took in the course of evaluating and approving the drug.
“We are concerned by apparent anomalies in F.D.A.’s processes surrounding its review of Aduhelm,” the committee chairs said in a 13-page letter asking for a raft of documentation and answers to questions.
“F.D.A. granted accelerated approval for the drug despite concerns raised by experts — including the agency’s own staff” and members of its independent advisory committee, the letter said.
“We are also concerned by reports of unusual coordination between F.D.A. and Biogen throughout the drug’s approval process,” the committee added.
The letter — addressed to the F.D.A.’s acting commissioner, Dr. Janet Woodcock, and signed by Representative Carolyn Maloney, chair of the House Committee on Oversight and Reform, and Representative Frank Pallone, chair of the House Energy and Commerce Committee — asks for information about virtually every step of the F.D.A.’s handling of Aduhelm, the brand name for aducanumab.
Citing details first reported in a New York Times investigation in July, the letter notes that two months before the drug was greenlighted in June, a council of senior F.D.A. officials “‘concluded that another clinical trial was necessary before approving the drug,’ with one member noting that approval could ‘result in millions of patients taking aducanumab without any indication of actually receiving any benefit, or worse, cause harm.’”
The approval of Aduhelm — a treatment requiring monthly intravenous infusions that Biogen has priced at $56,000 a year — has been met with a firestorm of criticism from many Alzheimer’s experts and other scientists.
While some Alzheimer’s experts did support the approval, given that there are so few therapies available for the devastating condition, many are concerned that the evidence does not convincingly show the drug can provide any benefit. There is also concern because the medication can cause brain swelling or brain bleeding.
The congressional letter also cites objections to the drug’s approval from a former Biogen senior medical director, Dr. Vissia Viglietta, who helped design the late-stage clinical trials of Aduhelm. She told The Times in July that the approval “defeats everything I believe in scientifically, and it lowers the rigor of regulatory bodies.”
Since the approval, some major medical centers — including the Cleveland Clinic, Mount Sinai Health System in New York City, and Providence, a large health system headquartered in Washington State — have decided not to offer Aduhelm to patients.
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And the Department of Veterans Affairs has decided not to include the drug in its formulary, a development first reported by Endpoints News, which quoted a spokesperson for the V.A. saying the decision was made “due to the risk of significant adverse drug events and to the lack of evidence of a positive impact on cognition.”
The letter from the committees says that on July 23, several days after The Times’s investigation was published, Dr. Woodcock and leaders of the agency’s Center for Drug Evaluation and Research provided a briefing to the congressional staff and materials including the minutes of the council meeting cited in The Times article.
“This information was helpful, but significant questions remain,” the letter said.
In a statement in response to the letter, the F.D.A. said it would work with Congress to respond to the requests for documents and information. It also noted that in July, Dr. Woodcock called for the Department of Health and Human Services’ Office of Inspector General to conduct an investigation of interactions between Biogen and agency officials.
“The F.D.A. recognizes the need for new therapies and used a science-based approach that incorporated consideration of patient perspectives in its evaluation of the benefits and risks of this therapy,” the statement said.
Controversy about aducanumab began when two nearly identical late-stage clinical trials of the drug were shut down in 2019 because an independent monitoring committee concluded that the drug did not appear to be helping patients.
A later analysis by Biogen found that participants receiving the highest dose of aducanumab in one trial experienced a very slight slowing of cognitive decline, but participants in the other trial did not benefit at all.
The committees’ letter includes several questions about the F.D.A.’s close collaboration with Biogen since that time, including several meetings a week in the summer of 2019 to jointly assess the data and chart a path toward approval, as well as a joint Biogen-F.D.A. presentation to an advisory committee of independent experts.
The letter also asks for information relating to an internal review the F.D.A. conducted this year to assess its collaboration with Biogen, an inquiry first reported by The Times. The committees are also seeking information about any meetings between Biogen officials and F.D.A. officials that were not formally documented with minutes or other notes.
“F.D.A. officials asserted during the July 23, 2021, staff briefing that it may also be commonplace for some of this communication to occur as informal discussion between F.D.A. and the drug sponsor,” the letter said.
“However, F.D.A. officials also acknowledged in the staff briefing that not all communication with Biogen officials was memorialized, counter to F.D.A.’s best practices.”
The F.D.A. has previously said that it “often works closely with industry,” especially “where there is a significant need for treatments for devastating diseases.”
Dr. Woodcock has publicly acknowledged “process problems,” but has not described what those problems were.
The letter also asks whether F.D.A. officials participated in projects or conference presentations with Biogen officials while the company had applications for drug approvals pending before the F.D.A.
The Times reported that while aducanumab was in clinical trials, Dr. Billy Dunn, director of the F.D.A. office that reviews Alzheimer’s drugs, and Samantha Budd Haeberlein, who oversaw the drug’s clinical development for Biogen, worked together on several other projects, including conference presentations.
In July, the committees sent a letter to Biogen requesting documents and information related to Aduhelm. When asked to comment about the investigation and the letter to the F.D.A., Biogen said in a statement on Thursday: “We are continuing to cooperate with the committees’ investigation and to produce documents in response to the committees’ requests.”
In written answers to questions from The Times in July, Biogen said, “Biogen stands 100 percent behind Aduhelm and the clinical data that supported its approval.”
In announcing its approval in June of Aduhelm — the first new drug for Alzheimer’s in 18 years — the F.D.A. acknowledged there was not sufficient evidence that the drug would help patients.
Instead, the agency said it was greenlighting Aduhelm under a program called “accelerated approval,” which allows the authorization of drugs without persuasive proof of benefit if they are intended to treat serious diseases with few treatment options and if the drug affects part of the disease’s biology (known as a biomarker) in a way that is “reasonably likely to predict clinical benefit.”
The reason the agency gave — that the drug reduces a key protein that clumps into plaques in the brains of people with Alzheimer’s — is one that the agency official leading the aducanumab review had said in an earlier public meeting would not be used.
Many Alzheimer’s experts say there is not nearly enough evidence that reducing the protein, amyloid, slows the progression of memory and thinking problems.
The letter from the congressional committees asks detailed questions about why the agency decided on accelerated approval and why, once it had decided to seriously consider that option in April, it did not go back to the council of senior officials or the advisory committee of independent experts to ask their opinion.
In November 2020, the independent advisory committee had been asked to consider only standard approval and had voted overwhelmingly that the evidence was not sufficient to show the drug worked. Three members of that committee resigned in protest in June after the drug was approved.
The letter also asks for documents concerning the process of deciding on the drug’s label. The label was widely criticized because it initially said the drug could be given to anyone with Alzheimer’s, and a month after approval, the agency sharply narrowed its recommendation and said that only patients in mild stages of the illness should receive it.
“Aduhelm’s approval has far-reaching implications, not only for individuals with Alzheimer’s, but also for seniors, federal health care programs, and future research, development, and approval of drugs for Alzheimer’s and other diseases,” the letter said, noting that women and people of color are disproportionately affected by Alzheimer’s.
“To help ensure that the American people continue to have the utmost confidence in F.D.A. and the safety and efficacy of approved drugs,” the letter added, “and to help inform future legislation, we need more information about F.D.A.’s process for reviewing and approving Aduhelm.”