The FDA, in a statement, said “the decision to approve Aduhelm was based on our scientific evaluation of the data contained in the application, which are described in the approval documents.”
Biogen, in a statement, said it “stands by the integrity of the actions we have taken.”
Conclusions of the FDA process: The committees’ review of interactions between the FDA and Biogen over nearly two years found that an internal agency review concluded that the FDA’s work on a briefing document with the drugmaker before a November 2020 advisory committee meeting “was not an appropriate approach” given the lack of consensus within the Office of New Drugs on the regulator’s position. Councilors overwhelmingly voted against recommending Aduhelm’s approval.
Committee staff obtained documents showing that FDA staff and Biogen officials held at least 115 meetings, calls, and “substantive email exchanges” from July 2019 to July 2020. The agency acknowledged that the total number of meetings during this period is unknown because the FDA had no “clear record” of informal interactions between regulators and the drug sponsor.
The FDA in its statement pointed to an internal review that concluded the actions were appropriate, and said the agency has already begun to implement changes consistent with the committee’s recommendations, including reviewing the use of a joint disclosure document.
But the agency has defended its practice of working with companies.
“It is the agency’s job to interact frequently with companies to ensure that we have adequate information to inform our regulatory decision-making,” the statement said. “We will continue to do so, as it is in the best interests of patients.”
The committees’ investigation also found that the FDA moved quickly to consider Aduhelm under the fast-track approval pathway after studying the drug for mainstream approval for nine months. The course correction follows negative feedback within the FDA about the level of clinical benefit the drug needed to show for mainstream approval, according to the report.
Biogen discoveries: The report revealed that Biogen was seeking a broad label indication – originally proposed by the FDA – for Aduhelm, even though it lacked clinical data on patients at any stage of the disease. Alzheimer’s Society team leaders have raised concerns about the lack of data to support the use of the drug outside of the disease stages studied in the trials. Biogen asked the FDA to restrict the label within one month of Aduhelm’s approval due to confusion between patient and supplier.
Biogen also initially set Aduhelm’s introductory price at $56,000 per year to make the drug “one of the best pharma launches ever,” knowing that the financial burden would fall primarily on Medicare. Internal company projections revealed that Medicare would represent more than 85% of Aduhelm’s target patient population at launch.
“We believed Aduhelm had the potential to provide a historic opportunity to turn the tide for Alzheimer’s patients and their families,” a company spokesperson said.
CMS limited coverage of the drug – and any similar ones under fast-track approval – in April to patients enrolled in a clinical trial confirming the drug’s effectiveness. If the FDA approved new amyloid-targeting drugs through its traditional process, the agency would cover them without the testing requirement.
Reaction: Committee staff concluded that the report raised “serious concerns” about the FDA’s adherence to its own internal protocols and Biogen’s “disregard for Aduhelm’s efficacy and access to approval process.” “. Staff recommended that the agency ensure that all interactions with drug sponsors are properly documented, establish guidelines on the use of joint briefing materials for advisory committee meetings, and update its guidelines for industry for the development and review of new drugs for Alzheimer’s disease.
“The FDA must take prompt action to ensure that its processes for reviewing future treatments for Alzheimer’s disease do not lead to the same doubts about the integrity of the FDA review,” the report said. .