The FDA said in a statement the “decision to approve Aduhelm was based on our scientific evaluation of the data included in the application as described in the regulatory materials.”
Biogen said in a statement it “stands by the integrity of the actions we are taking.”
Findings of the FDA process: The committees’ review of FDA and Biogen’s interactions over nearly two years found that an internal review by the agency concluded that FDA’s work on a briefing document with the drugmaker ahead of a November 2020 advisory committee meeting The lack of “not an appropriate approach” was consensus within the Office of New Drugs on the regulator’s position. The advisers voted overwhelmingly against recommending the approval of Aduhelm.
Committee staff obtained documents showing that FDA staff and Biogen officials held at least 115 meetings, phone calls and “substantive email exchanges” from July 2019 to July 2020, providing a “clear record” of the informal interactions between the regulatory authorities and the drug sponsor.
The FDA noted in its statement an internal review that found the measures appropriate and said the agency has already begun implementing changes in line with the committee’s recommendations, including considering the use of a common information document.
But the agency defended its practice of working with companies.
“It is the Agency’s responsibility to frequently interact with companies to ensure we have adequate information to make our regulatory decisions,” 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 quickly moved to consider Aduhelm under the accelerated approval process after spending nine months evaluating the drug for traditional approval. The course correction followed negative feedback from within the FDA about the level of clinical benefit the drug needed to have for traditional approval, the report said.
Biogen Results: The report noted that Biogen was pursuing a broad indication – originally proposed by the FDA – for Aduhelm despite a lack of clinical data on patients at all stages of the disease. The leaders of the company’s Alzheimer’s team expressed concerns that they lacked the data to support use of the drug outside of the disease states studied in studies. Biogen asked the FDA to restrict the label within a month of Aduhelm’s approval due to confusion between patients and vendors.
Biogen also initially set the introductory price for Aduhelm at $56,000 annually to make the drug “one of the best pharmaceutical launches of all time,” despite knowing that the financial burden would rest primarily on Medicare. Internal projections indicated that Medicare would account for more than 85 percent of Aduhelm’s target patient population at launch.
“We believe that Aduhelm has the potential to provide a historic opportunity to turn the tide for patients with Alzheimer’s disease and their families,” said a company spokesman.
CMS limited coverage for the drug — and any others like it that got the green light under accelerated approval — in April to patients participating in a clinical trial confirming the drug’s effectiveness. If the FDA approves new amyloid-targeting drugs using its traditional process, the agency would cover them without the testing requirement.
Reaction: The committee’s staff concluded that the report raises “serious concerns” about the FDA’s compliance with their own internal protocols and about Biogen’s “disregard for efficacy and accessibility in the approval process for Aduhelm.” Staff recommended the agency ensure that all interactions with drug sponsors are properly documented, provide guidance on the use of common briefing documents for Advisory Committee meetings, and update its industry guidance for the development and review of new Alzheimer’s drugs.
“The FDA must act quickly to ensure that its processes for reviewing future Alzheimer’s treatments do not raise the same doubts about the integrity of the FDA’s review,” the report said.