Aduhelm approval controversy dials up as FDA seeks probe


In another twist to the Aduhelm approval tale, FDA's Janet Woodcock has called for an independent investigation into the relationship between agency staffers and Biogen executives.

The acting FDA commissioner has sent a letter to the Department of Health and Human Services (HHS) inspector general Christi Grimm on Friday, asking for a review of the communications between the FDA and the company and the process that led to the approval of Aduhelm (aducanumab).

In the letter, she writes: "FDA's decisions are far ranging and it is inevitable that some of those decisions will lead to controversy."

However, she says that some of the interactions between the agency and Biogen "may have occurred outside the formal correspondence process [and] could undermine the public's confidence in FDA's decision".

The FDA cleared Aduhelm for marketing last month, making it the first treatment for the disease to be approved in nearly 20 years and also the first claimed to affect the underlying disease process in Alzheimer's. The decision came against the advice of the FDA's own expert advisors, three of whom have resigned as a result.

The letter follows the extraordinary situation in which Biogen and partner Eisai asked the FDA to restrict the label for Aduhelm, as the agency approved the drug for all Alzheimer's patients, not the mildly-affected population tested in clinical trials.

It also comes two weeks after STAT News reported "off the books" meetings between Biogen executives and FDA staffers including Office of Neuroscience director Billy Dunn.

That in turn has led prominent lawmakers – including Rep Frank Pallone of the Committee on Energy and Commerce and Rep Carolyn Maloney of the Committee on Oversight and Reform – to also seek a probe by HHS.

"We continue to have concerns about the approval process for Aduhelm, how Biogen set its price, and the implications for seniors, providers, and taxpayers," they said in a joint statement, adding: "An OIG review will complement our committees' robust investigation of this matter."

The letter is a change of tone from Woodcock, who initially backed the decision and said it was "a very solid accelerated approval."

Watchdog group Public Citizen is also asking that Woodcock's involvement in the Aduhelm approval should be investigated, and specifically whether she "fostered a culture within the FDA" that "permitted and encouraged such an inappropriate collaboration".

Woodcock was in charge of the FDA's Centre for Drug Evaluation and Research (CDER) at the time of the approval of Sarepta Therapeutics' Exondys 51 (eteplirsen) for Duchenne muscular dystrophy (DMD) in 2016, against the opinions of advisors and senior staffers at the agency.

Other criticisms of the FDA's review of Aduhelm include that it granted the drug a conditional approval, allowing it to be prescribed and used while Biogen conducts a post-marketing, phase 4 confirmatory study – which could take years to complete.

The accelerated approval also relied on merged data from two trials that failed independently, and used reduction of amyloid deposits as a surrogate marker for efficacy. Critics argue that other trials of amyloid-busting drugs have cleared plaques effectively but had no significant impact on cognition in Alzheimer's.