Health Letter, August 2021
By Michael Carome, M.D.
If you’re not outraged,
you’re not paying attention!
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Stunning new disclosures in a detailed exposé published by STAT on June 29 appear to provide further evidence of the unprecedented and inappropriately close collaboration that occurred between the Food and Drug Administration (FDA) and drugmaker Biogen long before the agency’s reckless decision to approve the company’s monoclonal-antibody drug aducanumab (marketed under the brand name ADUHELM) for the treatment of Alzheimer’s disease.
According to STAT, starting more than two years ago, key FDA staff in the Center for Drug Evaluation and Research’s (CDER’s) Office of Neuroscience (ON) who were responsible for the review of Biogen’s marketing application for aducanumab for treatment of Alzheimer’s disease began working closely with the company to analyze data from the key clinical trials of the drug. As explained in last month’s column, this unprecedented collaboration dangerously compromised the independence and objectivity of the agency’s review and approval of the drug.
Among the most troubling disclosures in the STAT exposé were the following:
- In early May 2019 — shortly after Biogen and its partner Eisai had announced the decisions to terminate the two pivotal phase 3 clinical trials testing aducanumab after a prespecified interim futility analysis and to end development of the drug — Biogen Chief Scientist, Al Sandrock, reached out to CDER’s ON Director, Dr. Billy Dunn, with whom he “already had a longstanding professional relationship,” and sat down with him for an “off-the-books” meeting while the two were attending a neurology conference in Philadelphia. “Sandrock wanted to let Dunn know that Aduhelm — publicly declared ineffective — might actually be slowing the progression of Alzheimer’s… And wanted to know if Dunn would be open to helping find a way to get the drug approved.”
- “‘It was clear that Billy Dunn was an ally, so the job for Biogen became figuring out how to support his efforts within the FDA,’ a former Biogen employee told STAT.”
- Following Sandrock’s meeting with Dunn, Biogen “mounted a secret campaign, code-named ‘Project Onyx,’ to resurrect the drug and convince the FDA to give it the green light. Central to their mission was an inside ally: Billy Dunn, the agency’s top regulator of Alzheimer’s drugs.”
- “The FDA’s support grew quickly. By June 2019, only a month after the crucial meeting with Dunn, agency officials in his Office of Neuroscience were so willing to advance Aduhelm that they proposed as one option a regulatory shortcut called ‘accelerated approval,’ according to meeting minutes read to STAT. The move stunned even Biogen’s top executives, who had considered that out of the question for a host of reasons, including the fact that the FDA had never used the [accelerated approval] pathway for an Alzheimer’s treatment.
“This disclosure contradicts what the FDA has said publicly in recent weeks about how it came to consider the use of accelerated approval for Aduhelm. An internal review document made public by the FDA last week claimed officials inside the agency first raised the possibility of an accelerated approval of Aduhelm during a meeting held this past March 31.”
- “To some inside Biogen, the FDA’s tone made approval seem inevitable.”
- “The signal of support provided by the FDA’s Dunn to Sandrock during their off-the-books meeting in early May 2019 triggered Project Onyx and the revival of Aduhelm. By mid-May, Biogen was sharing clinical data and other information with FDA officials.”
- “All of the investment that Biogen put into courting Dunn appeared to be paying off. Dunn’s Office of Neuroscience offered Biogen a road map to Aduhelm’s approval, suggesting five different scenarios or options for ways the drug could be reviewed by the agency to allow it to reach the market. Only one of those five options even contemplated Biogen having to conduct another clinical trial before approval. Three would result in the drug’s immediate approval.”
- “After the June 14, 2019, meeting [between Biogen and the FDA], Biogen and the FDA established a ‘working group collaboration’ consisting of company employees and agency review staff. The group met or communicated almost daily in June, July, and August of 2019, working to collect and analyze Aduhelm data for inclusion in the planned marketing submission. The group decided to pursue a standard FDA approval based on data on how patients had fared on cognitive surveys.”
- “‘I knew from the interest levels within FDA that the agency was always going to find a way to approve Aduhelm,’ said a former Biogen employee with knowledge of its interactions with Dunn and other FDA officials during this time period.”
The circumstances described in the STAT exposé paint a damning picture of FDA drug regulators who surrendered their independence and objectivity, essentially began working on behalf of Biogen and fostered regulatory capture at the agency.
The FDA’s decision to approve aducanumab was a disastrous blow to the agency’s credibility, public health and the financial stability of the Medicare program. It is imperative that the Department of Health and Human Services’ Office of Inspector General and Congress thoroughly investigate this decision and the circumstances that preceded it, including the inappropriately close collaboration between the FDA and Biogen that corrupted FDA’s review and decision-making process for the drug.