Federal watchdog will review the controversial FDA approval of Biogen’s Alzheimer’s drug

The federal watchdog at the Department of Health and Human Services will review the process used by the Food and Drug Administration to approve the Alzheimer’s drug sold by Biogen, which has caused unprecedented controversy over regulatory standards.

Specifically, the HHS Office of Inspector General will examine the accelerated approval pathway that the FDA increasingly uses to speed approvals for medicines to treat serious conditions and fill an unmet medical need. This was the pathway used by the agency two months ago when it OK’d the Aduhelm treatment for Alzheimer’s.

However, the agency endorsement is arguably the most controversial approval it has ever made and is generating intense scrutiny because of the circuitous path that Biogen took to convince FDA officials to greenlight the medicine. Consequently, acting FDA Commissioner Janet Woodcock asked the OIG to review the approval process. A consumer advocacy group made the same request.

Those requests followed a STAT report that Biogen launched a behind-the-scenes effort dubbed Project Onyx to convince FDA officials to approve its drug. The drug maker took this step in light of a complicated and confusing reanalysis of two clinical trials that initially cast doubt on Aduhelm’s efficacy.

Instead, the company reanalyzed the data and found that participants receiving the highest dose of the drug in one trial experienced a very modest slowing of cognitive decline, but participants in the other trial did not benefit at all. With potentially billions of dollars in sales at stake, Biogen targeted Billy Dunn, who heads the division that approved the drug and, therefore, was seen as a needed ally.

Consequently, the FDA played a proactive role in helping the company navigate the process, going so as far as drafting a road map on how the company could win approval. The disclosure, which experts have described as unusual, triggered outrage, especially after an FDA advisory panel of outside experts nearly unanimously recommended the drug not be approved at a meeting last fall.

Moreover, the panel was not told by the FDA that accelerated approval was an option being considered or that reducing amyloid, a protein in the brain that some believe slows memory and thinking, would be used as a surrogate marker for effectiveness. In fact, Dunn told the panel meeting last November that amyloid would not be used as a surrogate.

And so, the HHS OIG will review interactions between the FDA and “outside parties, as well as other aspects of the process, such as deciding on this pathway and scientific disputes,” the watchdog said. The review will extend to FDA policies and procedures, and determine whether the agency was in compliance by looking at a sample of drugs that were approved using the accelerated pathway. However, the OIG will not assess the “scientific appropriateness” of any of the drugs to be reviewed.

“We are committed to overseeing the integrity of FDA’s drug approval process, including the decisions informing how some drugs are selected for the accelerated approval pathway. Our planned work takes into consideration the concerns raised by stakeholders about FDA’s approval of the Alzheimer’s treatment drug Aduhelm,” an HHS OIG spokesperson said.

“As part of our comprehensive assessment, we will determine if the application of FDA’s pertinent policies and procedures allow for inappropriate relationships with pharmaceutical officials and other external entities. We are confident our findings and recommendations will provide meaningful information to stakeholders and promote optimal program administration at FDA.”

However, the report is not expected to be completed by 2023 and may be one of multiple reports HHS OIG issues as part of its review.

The approval has financial and health implications for millions of families, insurers, and American taxpayers. The wholesale list price is $56,000, greatly surpassing the $8,300 threshold that a nonprofit determined was the price at which the medication could be considered cost-effective. There are an estimated 5.3 million people 65 years and older in the U.S. with Alzheimer’s and another 200,000 younger patients with a form of the disease known as early onset.

Initially, the FDA issued a broad label for the drug, meaning it could be prescribed to anyone, but the agency later narrowed that to people with mild cognitive disease or mild Alzheimer’s. But the debate over effectiveness prompted Medicare to schedule a meeting to decide national coverage and some private health insurers are either withholding coverage or waiting to see what Medicare will decide, leaving many people in limbo.

In a brief series of tweets on Wednesday, Woodcock wrote that the FDA intends to “fully cooperate” with the review and “welcomes the opportunity to provide clarity” on the accelerated pathway. “We are committed to ensuring the integrity of the accelerated approval program. … Should the HHS OIG identify an actionable items and provide the agency with any recommendations, the FDA would review those expeditiously to determine the best course of action.”

The FDA, however, has publicly defended its approach to approving Aduhelm. In a July 28 letter to the New England Journal of Medicine, Dunn and three other high-ranking officials at the FDA division that approves medicines argued that the accelerated pathway was appropriate and there is clinical evidence that the drug can benefit some patients.

“The decision fits squarely in the accelerated approval pathway, which was created to allow patients with a serious or life-threatening disease earlier access to a potentially important treatment. As scientific knowledge evolves, so should our thinking, and it should be reflected in our decisions. We believe current knowledge was appropriately reflected in aducanumab’s approval,” they wrote.

In a statement, Michael Carome, who heads Public Citizen Health Research Group, praised the decision by the OIG. The consumer group had urged the watchdog to review the approval over what Carome called a “collaboration that dangerously compromised the independence and objectivity of the agency’s review of the drug.”