A scathing congressional report has detailed communications described as "inappropriate" and "atypical" between Biogen and the FDA regarding the approval of Alzheimer’s disease drug Aduhelm plus the decision-making behind the pricing and marketing of the now-benched medicine.
The staff report into the FDA and Biogen’s actions regarding Aduhelm was issued Thursday (PDF) by Oversight and Reform Committee Chairwoman Carolyn Maloney, D-New York, and Energy and Commerce Committee Chairman Frank Pallone Jr., D-New Jersey. The 18-month investigation has revealed the full extent of how the company and the regulatory agency worked together to push the therapy through the regulatory process despite dubious evidence to support the full breadth of the label it was ultimately approved for.
Among the many items in the bombshell report are details on how Biogen and the FDA worked together to prepare briefing documents for the advisory committee that ultimately voted against approving Aduhelm. According to the report, Biogen was provided with advance insight into the FDA's responses and direct guidance to draft its own sections. However, some sections were drafted by the FDA and then included in Biogen's portion of the document.
Despite the panel's recommendation, the FDA approved Aduhelm anyway. Several members resigned in protest. The FDA does not have to follow the recommendation of the committee but typically does heed the advice of the outside experts.
After the meeting was held in November 2020, nonprofit consumer rights group Public Citizen raised concerns about inappropriate communications between the FDA and Biogen.
The FDA conducted an internal review of the actions leading up to the advisory meeting but had never released the findings until today. According to that review, even the FDA acknowledged “the joint briefing document was not an appropriate approach in this instance.”
The report finds that the two parties held at least 115 meetings, calls and email exchanges over the 12 months beginning in July 2019. While it’s FDA protocol to document meetings between agency staff and companies sponsoring drugs, that was not followed, so the true volume of correspondence is unknown. The report identified another 66 calls and email exchanges that were not previously recorded by the FDA.
Aduhelm was approved under the accelerated review pathway, which allows a drug to enter the market based on biomarker evidence that is likely to predict clinical benefit. The report shows that the FDA originally considered a traditional approval, which would mean a nine-month timeline, but abruptly changed course after a three-week review and granted approval under the accelerated pathway.
Moreover, the FDA apparently pushed for a broad label indication that would allow the drug to be used in all Alzheimer's stages even though there were no data to support use beyond mild cognitive impairment and mild Alzheimer's. Biogen had internal reservations about the lack of evidence and an unknown safety profile but went along anyway.
And then there's the pricing. Biogen initially set the price for Aduhelm at $56,000 per year apparently to “make history” for the company with "one of the top pharmaceutical launches of all time," the report said. According to internal documents, the company saw the drug as an unprecedented financial opportunity with estimated potential peak revenue of $18 billion per year. Biogen developed what the report calls an aggressive launch and marketing plan to maximize revenue.
The report found that Biogen commissioned third-party consultants who suggested a price greater than $40,000 per year would maximize revenue while a price below $40,000 per year would limit payer and physician pushback.
The company knew that the cost of the new Alzheimer's drug would be a burden on Medicare and costly to patients. Biogen itself estimated that the drug would cost Medicare $12 billion for one year or 36% of the 2018 Part B budget. The company also apparently was aware that some Medicare patients would not be able to afford the drug.
In an effort to restore faith in the FDA's approval processes, the committee has recommended that the agency properly document meetings with drug sponsors, establish a protocol for joint agency-drug sponsor briefing documents to be presented at advisory committees and update existing guidance for industry regarding the development and review of new Alzheimer's drugs.
The report also includes recommendations for Biogen and other companies sponsoring drugs for approval, including clear communication to FDA on safety and efficacy concerns and more consideration of value assessments made by outside experts.
“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,” said Maloney in a statement.
Pallone similarly said that expediency must not take precedent over protocols that insure the FDA’s independence and scientific rigor.
“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,” Pallone said.
Aduhelm is still approved under the accelerated pathway, however, Biogen and its partner Eisai have moved on to the next generation therapy, lecanemab.
Editor's Note: The report has been removed from the committee website as of January 4, 2023, due to the change over in leadership of the House of Representatives.