Following an 18-month investigation, House of Representatives Oversight and Reform Committee Chairwoman Carolyn Maloney and Energy and Commerce Committee Chairman Frank Pallone Jr., released a report on the Food and Drug Administration (FDA) approval of Aduhelm, a controversial Alzheimer’s disease drug manufactured by Biogen, Inc.
As readers may recall, the FDA approved Aduhelm in June 2021 despite the advisory committee’s unanimous vote against the approval. While the FDA is not bound by the advisory committee’s recommendation, it has historically followed the advice of outside experts. As a result, several members of the advisory committee resigned in protest at the FDA’s approval. Additionally, not only did the advisory committee vote against the traditional approval, but experts within the FDA’s own Center for Drug Evaluation and Research Office of Biostatistics raised concerns about the inconsistency of the drug’s clinical data.
The report details the way Biogen and the FDA worked together to prepare briefing documents for the advisory committee, including that Biogen was allegedly provided advance insight into the FDA’s responses. According to the report, Biogen and the FDA communicated through more than 100 calls, meetings, and emails from July 2019 to July 2020. While the FDA has guidance that indicates the agency should document “substantive interactions,” such as meetings between agency staff and the companies that are sponsoring drugs for approval, not all meetings and correspondence were documented in this case, with an additional 66 calls and emails that were not recorded by the FDA uncovered by the Committees’ investigation. Therefore, it is difficult to know the true volume of correspondence and communication between the two entities.
The report also shows that the FDA originally considered Aduhelm under a traditional approval, but after a three-week review, the agency opted to grant approval under the accelerated review pathway. The accelerated review pathway is available to drugs and is based on biomarker evidence that is likely to predict clinical benefit.
Not only did the FDA change the pathway under which the drug was approved, but it also seemed to push for a broad label indication than Biogen initially wanted. According to the report, the FDA pushed for a broad label indication that would allow the drug to be used in all Alzheimer’s stages, despite the lack of evidence to support its use beyond mild Alzheimer’s and mild cognitive impairment. Biogen had some internal reservations about the push for broad indication but ultimately went along with the FDA’s plan.
Finally, regarding the pricing of the drug, Biogen set the initial price of Aduhelm at $56,000 per year, despite recommendations from third-party consultants of around $40,000. Biogen also noted that at that price, Aduhelm would be a burden to Medicare and costly to patients but disregarded that to financially “make history” for the company.
Report Recommendations
The report makes several recommendations for the agency, to re-establish faith in the FDA’s approval processes. Some of the recommendations include a requirement that the FDA properly document all meetings and communications with drug sponsors, establish a protocol for joint agency-drug sponsor briefing documents to be presented at advisory committee meetings, and to update the existing guidance for industry regarding the development and review of new Alzheimer’s drugs.
The report also made recommendations for Biogen and other sponsor companies, including clearly communicating with the FDA on safety and efficacy concerns they may have, as well as more seriously considering the value assessments made by outside experts.
Congressional Response
“I am hopeful these findings are a wake-up call for FDA to reform its practices and a call to action to my Congressional colleagues to continue oversight of the pharmaceutical industry to ensure they don’t put profits over patients,” Chairwoman Maloney said in a statement.
“While we all support the search for new cures and treatments to address devastating diseases like Alzheimer’s, we must ensure that expediency does not take precedence over protocols that ensure the independence and scientific rigor of FDA. Patient safety and drug efficacy must remain at the core of our nation’s pharmaceutical regulatory review process. FDA must continue to take corrective actions to re-earn the trust of the American people, and Biogen and other pharmaceutical manufacturers must also learn from the issues outlined in this report and implement our recommendations to place the well-being of patients over profits,” Chairman Pallone said.
Links
For a link to the Committees’ full report, click here.
For a link to select investigation documents from the FDA, click here.
For a link to select investigation documents from Biogen, click here.