Janet Woodcock, MD, acting commissioner of the FDA, called for an inquiry by the Office of the Inspector General into possible interactions between agency officials and Biogen that "may have occurred outside of the formal correspondence process."
Today, the acting commissioner of the FDA, Janet Woodcock, MD, announced that she is requesting an independent review and assessment of the interactions between representatives of Biogen and the agency during the process that led to the approval of the company's controversial Alzheimer disease treatment, aducanumab (Aduhelm), to be conducted by the Office of the Inspector General of the Department of Health and Human Services.1
“We believe an independent assessment is the best manner in which to determine whether any interactions that occurred between the manufacturer and the agency’s review staff were inconsistent with FDA’s policies and procedures. We believe this review and assessment will help ensure continued confidence in the integrity of FDA’s regulatory processes and decision-making,” Woodcock wrote in a thread of tweets on her Twitter account, @DrWoodcockFDA (FIGURE).
Her letter to the Inspector General noted the significant attention and controversy that has followed this agent since Biogen’s 2019 about-face submission to the agency after discontinuing the 2 pivotal phase 3 trials, EMERGE (NCT02484547) and ENGAGE (NCT02477800), as well as a phase 2 safety study, EVOLVE (NCT03639987). Woodcock also noted that she has “tremendous confidence in the integrity” of the agency’s staff and leadership at the Center for Drug Evaluation and Research, and their need to remain unbiased in their decision-making.
Although, she pointed out the contact between aducanumab’s developer, Biogen, and the agency during the process of the review, some of which she wrote “may have occurred outside of the formal correspondence process.” As these concerns could “undermine the public’s confidence” in the decision to approve aducanumab, she wrote that conducting an investigation into any potential interactions that were inconsistent with FDA policy and procedure is essential.
The request for inquiry appears to stem in part from reporting from Stat, which last month noted an informal meeting in May 2019 took place between Alfred Sandrock Jr., MD, PhD, head of research and development, Biogen, and Billy Dunn, MD, Deputy Director, FDA Neuroscience Office, at a conference in Philadelphia, Pennsylvania.2
“If [the Office of the Inspector General] decides to conduct the review, the agency will fully cooperate & should they provide the agency with any recommendations, FDA would review expeditiously to determine the best course of action,” Woodcock tweeted, closing the thread with “The trust of the American public, especially during these difficult times is of the utmost importance to the FDA—and we will continue to exercise transparency around our decision-making as allowed by the law.”
Many have called into question the FDA’s decision to approve the Biogen agent, with much of the concern focused on the complicated and complex nature of both the submission process for the drug, the accelerated approval pathway that was utilized to OK the drug, and its potential clinical benefit for patients. After Biogen’s decision to reverse course and submit the agent, it presented data at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) annual meeting, December 4–7, 2019 in San Diego, California, that included an analysis from EMERGE and a post hoc analysis of a subset of patients who received high-dose treatment in ENGAGE were presented, suggesting that there were statistically significant changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores, with P values of .010 or .031 based on cutoff dates.
Additionally, the FDA’s own advisory committee, which convened to review the data in November 2020, recommended not to approve aducanumab, and since its approval, a number of members of that Peripheral and Central Nervous System Drugs Advisory Committee have resigned from their positions.
This news comes just days after the FDA announced an updated label for the antiamyloid therapy, which included updates to the Indications and Usage section of the 100 mg/mL injection’s label. That updated language states that treatment with aducanumab should be initiated in patients with mild cognitive impairment or mild dementia stages of the disease, the population in which the treatment was initiated in clinical trials. It continues to state that there are no safety or efficacy data on initiating treatment at earlier or later stages of the disease than were studied.3
Additionally, this also followed an updated review from the Institute for Clinical and Economic Review (ICER), which suggested that Biogen must drastically reduce the price of its newly approved anti-amyloid agent for the treatment of Alzheimer disease (AD), aducanumab (Aduhelm), in order for the therapy to be considered cost-effective for patients. The current list price of aducanumab has been set at $56,000 annually.4 ICER’s new report affirmed its prior publication in May, which suggested that in order for the agent to be cost-effective, its price would be between $2500 and $8300 per patient per year. When calculating the price based on assumed "optimistic" treatment benefits—relying only on the results of the positive study—the price would need to be between $11,100 and $23,100 for it to be considered cost-effective. Based on an assumption of "conservative" treatment benefits, the cost-effective range was reduced to between $1200 and $4200.5
The NeurologyLive Mind Moments podcast recently featured a number of experts in AD to inquire about their reactions to aducanumab’s approval in Episode 39, "A Controversial FDA Decision." It features insights from a number of individuals in the Alzheimer disease space, including neurologists, psychiatrists, and advocacy partners, including Marwan Sabbagh, MD; Anton P. Porsteinsson, MD; David Knopman, MD; Lon Schneider, MD, MS; Robert Howard, MD, MRCPsych; Ian Kremer, JD; and Douglas Scharre, MD, who shared their varying and nuanced opinions on this decision to better understand not only what this approval means for clinical care, but what the downstream effects of it may be. Listen to their varying insights below.