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The FDA broke with its own protocols in reviewing and subsequently approving Alzheimer's drug aducanumab (Aduhelm), by inappropriately collaborating with drugmaker Biogen on briefing documents, holding unreported meetings, and failing to gain internal consensus before engaging in such collaborations, according to an of the interactions between the agency and the drugmaker.

The report, from the House Committee on Oversight and Reform and the House Committee on Energy and Commerce, also questioned the agency's decision to "abruptly" switch to the accelerated approval pathway from the traditional approval pathway and to grant approval in the drug's label to a broad patient population.

The investigation involved multiple briefings with the FDA and review of more than 500,000 documents, including internal Biogen strategy documents, launch plans, materials from Biogen's board of directors, communications between Biogen and FDA leaders, and internal FDA correspondence. The Committees also examined the FDA's internal review of its interactions with Biogen ahead of and during a key advisory meeting.

Background

The FDA granted aducanumab accelerated approval on June 7, 2021. That action was clouded by Biogen's earlier decision to terminate trials of aducanumab in March 2019 after an interim analysis of trial data, the House Committees noted. Also muddying the waters was the fact that no member of the FDA's advisory committee voted in support of the data presented about aducanumab.

Within the FDA itself, biostatisticians had raised concerns regarding "the inconsistency of the drug's clinical data," according to the Committees' report.

In January 2022, Medicare announced that aducanumab and other monoclonal antibodies targeting amyloid beta in Alzheimer's disease would only be covered if patients were enrolled in qualifying clinical trials.

Summary of Report Findings

The FDA and Biogen developed a "working group" to examine the company's clinical trials, which led to at least 40 working group meetings and over 115 other meetings, calls, and "substantive" email exchanges from July 2019 to July 2020, according to the Committees' report. However, at least 66 calls and email exchanges among the FDA and Biogen working group were not properly documented, the Committees found.

The agency also chose to collaborate on a joint FDA-Biogen briefing document that was later presented at an advisory committee meeting, although such collaboration had been used in the past mainly for oncological drugs and "under circumstances of broad consensus." Both the Committees' investigation and a separate FDA internal review concluded that decision was "not an appropriate approach," given clashing views of the drug within the agency.

Documents reviewed by the Committees also suggested the agency "abruptly changed course" in granting approval under that accelerated approval pathway rather than the traditional approval pathway following "unfavorable feedback" for the traditional pathway during an expert council meeting.

The Committees' investigation also brought to light a number of concerns related to Biogen's "aggressive launch and marketing plans." Documents they obtained show the company estimated a peak revenue of $18 billion per year. The company set an initial price of $56,000 for treatment per year, despite what the Committees described as "a lack of demonstrated clinical benefit in a broad population."

Company documents suggested Biogen knew the high price would trigger "pushback" from payers and providers. "Biogen developed an external narrative about the drug's value to sell to the patients and the public," the report stated.

Internal company documents showed Biogen knew its high price would weigh heavily on Medicare and Medicare patients. A November 2020 presentation included an estimate of aducanumab costing the Medicare program $12 billion over the span of 1 year. A Biogen analysis also found Medicare patients could incur out-of-pocket costs for aducanumab that could account for as much as 20% of their income.

In its long-term plans, Biogen estimated it would spend more than $3.3 billion on sales and marketing for aducanumab from 2020 to 2024, more than double what the company spent on the drug's development from 2007 to its approval in 2021.

Recommendations

In response to the findings, the Committees urged the FDA to commit to taking certain measures in the future "to help restore the American people's trust in the agency's processes and assurances of drug safety and efficacy."

This included properly documenting "all substantive FDA interactions with drug sponsors," developing a protocol to address joint briefing documents between FDA and drug sponsors for advisory committees, and updating the agency's industry guidance for developing new Alzheimer's drugs.

The Committees noted the agency's internal review included similar recommendations about meeting documentation and joint briefing documents. The FDA reported such changes were "still in process" as of August 2022.

The Committees also called on Biogen and other drug companies to "communicate safety and efficacy concerns clearly" to the FDA in the future and to "consider the value assessment made by outside experts including patient access, when setting drug prices."

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