The FDA, in a statement, said that “the decision to approve Aduhelm was based on our scientific evaluation of the data contained in the application, which are described in the approval materials.”
Biogen, in a statement, said it “stands by the integrity of the actions we have taken.”
Results of the FDA process: The committees’ review of the nearly two-year interactions between the FDA and Biogen found that an internal agency review concluded that the FDA’s work on a briefing paper with the drugmaker before a committee meeting advisory in November 2020 “was not an appropriate approach” given the lack of consensus in the Office of New Medicines on the regulator’s position. The advisers voted overwhelmingly 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” between July 2019 and July 2020. The agency acknowledged that the total number of meetings in this period is unknown because the FDA did not have a “Clear Record” of informal interactions between regulators and the drug’s sponsor.
The FDA in its statement pointed to an internal review that found the actions were appropriate and said the agency has already begun implementing changes consistent with the committee’s recommendations, including examining the use of a joint information document.
But the agency defended its practice of working with companies.
“It is the agency’s job to interact frequently with businesses to ensure we have the right information to inform our regulatory decision-making,” the statement said. “We will continue to do this as it is in the best interest of patients.”
The committees’ investigation also found that the FDA moved quickly to consider Aduhelm under the accelerated approval pathway after studying the drug for traditional approval for nine months. The course correction followed negative feedback from the FDA about the level of clinical benefit the drug needed to show for traditional approval, according to the report.
Biogen meetings: The report found that Biogen was seeking a broad label indication, originally proposed by the FDA, for Aduhelm, even though it lacked clinical data on patients at all stages of the disease. Leaders of the company’s Alzheimer’s team expressed concern that they lacked data to support the drug’s use outside the stages of the disease studied in the trials. Biogen asked the FDA to reduce the label within a month of Aduhelm’s approval due to patient and provider confusion.
Biogen also initially set Aduhelm’s launch price at $56,000 a year to make the drug “one of the biggest pharmaceutical launches of all time,” despite knowing that the financial burden would fall primarily on Medicare. Internal company projections found that Medicare would account for more than 85 percent of Aduhelm’s target population at launch.
“We believe Aduhelm has the potential to provide a historic, game-changing opportunity for Alzheimer’s disease patients and their families,” a company spokesman said.
CMS limited coverage of the drug — and all similar ones green-lighted under accelerated approval — in April to patients enrolled in a clinical trial confirming the drug’s effectiveness. If the FDA approves new drugs targeting amyloid under its traditional process, the agency would cover them without the testing requirement.
Reaction: Committee staff concluded that the report raises “serious concerns” about the FDA’s adherence to its own internal protocols and about Biogen’s “disregard for efficacy and access in the Aduhelm approval process “. The staff recommended that the agency ensure that all interactions with drug sponsors are properly documented, establish guidance on the use of joint briefing documents for advisory committee meetings, and update its industry guidelines to develop and review new drugs for Alzheimer’s.
“FDA must take swift action to ensure that its review processes for future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA review,” the report said.