Woodcock calls for investigation into Aduhelm approval

Regulatory NewsRegulatory News | 09 July 2021 |  By 

The US Food and Drug Administration’s acting head has called on the Inspector General at the Department of Health and Human Services to conduct an investigation into matters related to the agency’s recent controversial approval of Biogen’s new Alzheimer’s disease drug Aduhelm (aducanumab).
Janet Woodcock, acting director of the US Food and Drug Administration (FDA), took to Twitter early Friday afternoon to make the announcement, sharing the letter she sent to Christi Grimm, acting inspector general at HHS.
“Given the ongoing interest and questions, today I requested that @OIGatHHS conduct an independent review and assessment of interactions between representatives of Biogen and FDA during the process that led to the approval of Aduhelm,” said Woodcock in her tweet, tagging the HHS Office of Inspector General.
In a Twitter thread, Woodcock noted that she believes the “independent assessment” will afford the best way to determine “whether any interactions that occurred between the manufacturer and the agency’s review staff were inconsistent with FDA’s policies and procedures.”
Woodcock’s letter is included in her tweets. In it, she refers to the “significant attention and controversy” surrounding the entire review process for the Aduhelm biologics license application (BLA), including “an ongoing focus” on how FDA staff interacted with Biogen representatives throughout the review process.
In the letter, the acting director seeks an outside determination from Grimm’s office of whether interactions between Biogen and FDA staff relating to the Aduhelm BLA “were inconsistent with FDA policies and procedures.”
Though Woodcock expressed “tremendous confidence” in the integrity of staff and leadership at FDA’s Center for Drug Evaluation and Research (CDER), she notes that particular focus has been placed on the possibility of contacts between Biogen and FDA that “may have occurred outside of the formal correspondence process.”
The health news outlet STAT reported in late June that Biogen had used “an FDA back channel” to aid in securing accelerated approval of the drug. In addition to reporting that back-channel meetings had occurred, STAT also reported that internal meeting minutes dating to June 2019 contained discussion of an accelerated approval pathway for Aduhelm – an option not put before the Peripheral and Central Nervous System (PCNS) drugs advisory committee at the November 2020 meeting that reviewed Aduhelm.
At that time, the committee handed FDA a resounding thumbs down to Aduhelm, citing lack of evidence of efficacy, concerns about frequent brain inflammation and bleeding in trial participants, and reliance on post hoc analysis of trial data to find signs of clinical improvement in Alzheimer’s disease patients. (RELATED: Adcomm gives big thumbs down to aducanumab, Regulatory Focus 06 November 2020)
STAT’s report that FDA considered accelerated approval of Aduhelm based on a surrogate endpoint of reduction in brain beta amyloid plaque as far back as 2019 “contradicts what the FDA has said publicly in recent weeks about how it came to consider the use of accelerated approval for Aduhelm,” according to STAT’s 29 June article. (RELATED: FDA approves aducanumab for use in Alzheimer’s disease, Regulatory Focus 07 June 2021)

In the wake of FDA’s unexpected accelerated approval for Aduhelm, three members of the PCNS advisory committee resigned in protest over the agency’s actions. 

Aaron Kesselheim, professor of medicine at Harvard Medical School and director of the school’s Program on Regulation, Therapeutics and Law (PORTAL), was among those who left the committee.

When asked his opinion about the investigation, Kesselheim told Focus that the investigation should stretch back to March 2019, when the aducanumab clinical trial program was halted after a futility analysis. In October 2019, Biogen reversed course and announced a plan to file a BLA for the drug when a reanalysis of data showed modest clinical benefit in a subset of patients.   

"I think an independent and public review of the entire aducanumab decisionmaking process dating back to the steps taken after the futility declaration would be a good idea to figure out where things went awry," said Kesselheim.

Physicians, patient groups, researchers, and insurers have all addressed the clinical and economic implications of having an Alheimer’s treatment with uncertain benefit, frequent serious side effects, and a $56,000 annual price tag.
Woodcock’s announcement comes the day after FDA announced additional labeling language indicating that Aduhelm is indicated for the treatment of people with mild cognitive impairment or mild dementia from Alzheimer’s disease, rather than the broader original language that appeared on the first label, issued just a month earlier. (RELATED: FDA trims Aduhelm's indicated population, Regulatory Focus 08 July 2021)
Citing “the continued public interest in this matter,” Woodcock’s letter asks for a speedy review of the Aduhelm situation, giving Grimm her assurance that any actionable items will be addressed.
Janet Woodcock


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Tags: biologics, CDER, ethics, FDA, US

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