FDA's Accelerated Drug Approval Process Under Investigation by OIG

Kerry Dooley Young

August 05, 2021

A federal watchdog group has announced it will conduct a broad assessment of how regulators approved certain medications, including aducanumab, the controversial drug for Alzheimer's disease (AD) that was recently approved with limited evidence of potential benefit.

The Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS) announced that it will be conducting a review of the accelerated approval process. Through this approval pathway, the US Food and Drug Administration (FDA) approves drugs on the basis of signals such as biomarker data that suggest that a medication may have real-world benefit for patients.

The review outlined by OIG will include an examination of how the FDA interacted with what it terms "outside parties." OIG said its recommendations about the FDA's accelerated approval pathway will be based on assessments of a sample of drugs that have been approved in this way. These drugs will include aducanumab (Aduhelm), which is used for AD.

"The FDA's approval of Aduhelm raised concerns due to alleged scientific disputes within the FDA, the advisory committee's vote against approval, allegations of an inappropriately close relationship between the FDA and the industry, and the FDA's use of the accelerated approval pathway," OIG said.

OIG said it would not assess "the scientific appropriateness" of any of these FDA approvals. There could be multiple reports from this investigation, it noted.

Acting FDA Commissioner Janet Woodcock, MD, said in a series of tweets Wednesday that the agency would cooperate with the OIG's review.

"Should the HHS OIG identify any actionable items and provide the agency with any recommendations, the FDA would review those expeditiously to determine the best course of action," Woodcock said.

The plan outlined by OIG may exceed the request Woodcock made public via Twitter on July 9.

In the letter Woodcock posted on Twitter, she asked for "an independent review and assessment of interactions between representatives of Biogen and the FDA during the process leading to the decision to approve [Aduhelm] to determine whether any of those interactions were inconsistent with FDA policies and procedures."

Woodcock also expressed her "personal commitment" that the FDA would fully cooperate with the OIG.

On Wednesday, Woodcock tweeted: "We are committed to ensuring the integrity of the accelerated approval program, which is designed to bring safe and effective drugs to patients with unmet medical needs as quickly as possible." She also said that the "FDA intends to fully cooperate."

https://twitter.com/DrWoodcockFDA/status/1422957203842023424?s=20

As reported by Medscape Medical News, the controversy over the approval of aducanumab has drawn attention to the ongoing absence of a confirmed FDA commissioner. Woodcock, who is a veteran FDA official, has both strong opponents who have asked President Joe Biden to give the agency a new leader and strong backers who have sought to have her confirmed as commissioner.

Persistent Doubts

Among the FDA's chief critics has been the nonprofit group Public Citizen. In June, Public Citizen called for HHS to remove Woodcock and other top FDA officials because of concerns over the approval of aducanumab.

In a Wednesday statement, Michael Carome, MD, director of Public Citizen's Health Research Group, welcomed the OIG announcement about the review of the FDA's accelerated approval pathway.

"Such an independent review is long overdue. We are particularly pleased that the OIG's evaluation will include an examination of the interactions between the FDA and outside parties during the review and approval process of these drugs," Carome said in a statement.

"In the case of aducanumab, the unprecedented, inappropriately close collaboration between the FDA and Biogen before and after the company submitted its marketing application for the drug dangerously compromised the independence and objectivity of the agency's review," Carome added.

A June news story that was published in STAT sparked broader concern about how closely the FDA and Biogen worked together to find a pathway to aducanumab's approval.

In a July 22 statement addressing concerns about aducanumab, Biogen said it would "welcome a formal review" of its interactions with the FDA about aducanumab. In this statement, Alfred Sandrock, MD, PhD, Biogen's head of research and development, complained that the drug has been "the subject of extensive misinformation and misunderstanding."

The accelerated approval of aducanumab was based on a reduction in "amyloid beta plaques, a surrogate biomarker that is reasonably likely to predict clinical benefit," Sandrock said in the statement.

The FDA gave Biogen until 2030 to prove aducanumab is effective in preventing progression of AD.

Certain agency officials and Biogen staff have essentially held that data from EMERGE, one of two paired phase 3 trials, can be read as a sign that aducanumab can keep AD progression at bay.

However, last year, members of an FDA advisory panel came to a different conclusion. Members of the Peripheral and Central Nervous System Drugs Advisory Committee and other critics said it was as likely that the companion ENGAGE study, seen broadly as a failed trial, was correct. Critics had called for more studies, at a minimum, before approval of the drug.

Those seeking more detailed information on aducanumab had a disappointment in late July when the news site Axios reported on delays with the publication of aducanumab study results.

Axios reported that The Journal of American Medical Association had requested edits of a paper about aducanumab trial results. The news site said Biogen told it that it had withdrawn the paper and had decided to pursue other publication opportunities.

Another source of detailed information on medical studies, the ClinicialTrials.gov, has not yet posted results for EMERGE (NCT02484547) and ENGAGE (NCT02477800).

The ClinicalTrials.gov website said results were submitted for both studies on July 1, 2021, and were returned on July 21, 2021, after a quality control review.

The Institute for Clinical and Economic Review (ICER) is slated to release a report today about the drug, according to the organization's website. Last month, a panel of ICER advisers said that aducanumab had no clinical benefit. ICER is an independent organization whose work influences insurers' policies for medication coverage.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She is the core topic leader on patient safety issues for the Association of Health Care Journalists. Young earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the Food and Drug Administration for Bloomberg. Follow her on Twitter at @kdooleyyoung.

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