Public Citizen Calls For Investigation Into Collaboration Between FDA and Biogen Over New Alzheimer’s Drug

A government watchdog group is calling for an investigation into the U.S. Food and Drug Administration’s handling of a new Biogen Alzheimer’s disease drug, saying the agency was dangerously cozy with the drug manufacturer.

In a December 9 letter (PDF) to the U.S. Department of Health and Human Services’ Office of Inspector General, Public Citizen called for the office to look into what it calls an “inappropriate close collaboration” with Biogen by FDA drug approval reviewers. According to the letter, the close relationship, which began before the company’s biologics license application (BLA) seeking approval for a proposed drug known as aducanumab, could have compromised the agency’s judgment.

Aducanumab is a drug under development by Biogen as a potential Alzheimer’s disease treatment. It is an experimental recombinant human monoclonal antibody targeting amyloid-β multimers.

Public Citizen indicates the pharmaceutical industry has tried 22 times over the past 20 years to pursue similar drugs for Alzheimer’s treatment, all of which have failed. The group says those drugs, like aducanumab, are based on an unproven “amyloid hypothesis” introduced in the early 1990s which rests on the premise that amyloid plaque deposits in the brain cause neuronal degeneration linked to Alzheimer’s disease.

The letter indicates aducanumab is likely no different. In fact, Biogen and Eisai, which were working on the drug together, issued a press release in March 2019 announcing they were abandoning the phase 3 trials after an interim analysis found those trials were unlikely to show the drug actually worked.

Development of the drug should have ended there, Public Citizen claims. Instead, the drug is up for approval with a glowing review from the FDA. According to Public Citizen, the review was the result of the FDA and Biogen working together to cherry-pick data from the clinical trials, despite the drug’s failure to perform.

In October 2019, Biogen announced plans to seek approval of aducanumab for patients with early signs of Alzheimer’s disease after reportedly conducting new analyses of data from previous studies in cooperation with the FDA. Biogen applied for a BLA in July 2020, and on November 4, the FDA posted a briefing document for its Peripheral and Central Nervous System (PCNS) Drugs Advisory Committee.

“Disturbingly, the primary briefing document was a 139-page document written jointly by the FDA and Biogen,” Public Citizen notes. “Most of the primary briefing document content appears to have been written by Biogen.”

The document revealed the FDA and Biogen had been working together since at least June 2019, following the company’s decision to abandon the Phase 3 trials, when the FDA told Biogen the best way to look at the earlier data was a “bilateral effort involving the Agency and sponsor”, according to the letter.

However, it did not reveal that the agency’s lead statistical reviewer, Dr. Tristan Massie, had his own objections to the methodology being used to promote the drug as effective.

“The totality of the data does not seem to provide sufficient evidence to support the

efficacy of the high dose,” Massie wrote in his review. “There is much inconsistency and no replication.”

That analysis did not find its way into the briefing documents provided by the FDA, according to Public Citizen.

Public Citizen warns this represents an unprecedented, and dangerous, level of cooperation between the FDA and a drug manufacturer in order to get a drug, which has already been shown to be ineffective, onto the market.

“Although we understand that it is not unusual for the FDA to meet with sponsors and provide advice regarding the development of drugs, the design of clinical trials, and the statistical analyses of trial data, among other things, the close collaboration that occurred between the agency and Biogen in conducting post hoc analyses of data from the aducanumab clinical trials is, to our knowledge, unprecedented,” the Public Citizen letter warns. “Typically, sponsors conduct their own detailed statistical analyses of clinical trial data supporting NDAs and BLAs, and the FDA then conducts its own independent analyses of the data following submission of these applications for approval. Such appropriate separation between the clinical trial data analyses conducted by the sponsor and those conducted by the FDA is critical to maintaining the independence and integrity of the FDA’s review of the data.”

The letter calls for the Office of Inspector General to launch a formal investigation into that relationship, which Public Citizen says has dangerously compromised the independence and objectivity of FDA staff, including senior staff and clinical reviewers.

The drug has not yet been approved for sale.