Woodcock expressed “tremendous confidence in the integrity of the staff and leadership” involved in the approval and their commitment to “unbiased and science-based decision-making.” But she said an independent review was important to answer questions that might undermine public confidence in the agency’s decision. On Twitter, where she announced her request, she pledged to cooperate fully if the inspector general decides to conduct the review.
The letter was the newest development in the saga of Aduhelm, a monoclonal antibody that breaks up toxic amyloid clumps in the brain. The drug’s approval on June 7 unleashed a torrent of criticism from lawmakers and scientists who argue there is scant evidence that the drug, which carries a list price of $56,000 a year per patient, helps patients.
But the agency’s approval had brought plaudits from some doctors and Alzheimer’s groups who say desperate patients need new treatments against the progressive, terminal illness. They predicted a surge of interest in the field. Aduhelm is the first Alzheimer’s medication cleared since 2003.
Earlier this week, the FDA changed the prescribing instructions for the drug, known generically as aducanumab, to limit it to patients with early-stage Alzheimer’s disease. That was a response to an outcry from doctors and others that the original label, which said the drug could be used for anyone with Alzheimer’s disease, was too broad.
“So many aspects of the approval of this drug have been remarkable, and this is another remarkable aspect of the process,” said Rachel Sachs, a professor at Washington University in St. Louis School of Law. “This is not typical of how the FDA moves through its procedures at so many different points. I think it is very important to have more information about how this decision was made.”
Caleb Alexander, an epidemiologist at Johns Hopkins Bloomberg School of Public Health and a member of an FDA advisory committee that last fall urged the agency to reject the drug, said the approval “has brought a new surprise every week.” He added that the relationship between the agency and Biogen “continues to be shrouded and more needs to be learned.” He said it was important for millions of Alzheimer’s patients to learn more as soon as possible.
In a statement, Biogen said, “We will, of course, cooperate with any inquiry in connection with a possible review of the regulatory process.”
Stat, a news site covering medical and science news, reported last month that Biogen waged a secret effort, dubbed “Project Onyx,” to secure FDA approval for the drug after it stumbled badly in clinical trials. The site said there was an informal meeting in May 2019 between Alfred Sandrock Jr., a top Biogen official, and Billy Dunn, the head of the FDA’s neuroscience office, at a conference in Philadelphia.
At that time, company officials had halted trials of the drug but were analyzing additional data and beginning to believe that the drug might be beneficial after all. Stat also reported that the FDA early in the approval process mentioned several possible paths to clearance, including one called accelerated approval — even though officials told an outside advisory committee later that the option was not under consideration.
Biogen declined to comment on the Stat report. Dunn did not respond to an email seeking comment.
It may seem odd for officials to request inspector general investigations into their own agencies or departments, but it is not uncommon, according to experts on the federal government. The request allows officials to respond to criticism about a complicated and contentious issue — especially one that involves public trust — and to distance themselves from the controversy. But an inspector general investigation into an FDA drug approval is highly unusual.
Woodcock is in an especially sensitive position. She has been considered among the front-runners to be nominated by the Biden administration to become permanent FDA commissioner. But the White House has not nominated her — and it is not clear that it will — because of opposition from a handful of Senate Democrats, including Sen. Joe Manchin III of West Virginia. They say the FDA, with Woodcock running the drug division, for years approved too many opioids, fueling the epidemic. Woodcock’s supporters reject that, saying the opioid epidemic has had many causes, including physicians who overprescribed pain pills.
Demands for investigations into the Aduhelm approval have been multiplying. Public Citizen, a watchdog group that frequently criticizes FDA, had called for an inspector general investigation late last year, saying the FDA and Biogen worked together to salvage the drug and “jointly relied on dubious analyses” that overemphasized the possibility of a benefit. The group pointed out that the FDA and Biogen co-authored a joint briefing document for the advisory committee meeting.
On Tuesday, Rep. Katie Porter (D.-Calif.) called for the inspector general to investigate the approval. Earlier, two House committee chairs vowed to look into the situation.
Much of the uproar over the approval has centered on the FDA’s use of accelerated approval to clear the drug after concluding there was not enough evidence of clinical effectiveness for a full approval. In two large clinical trials for early-stage patients, Biogen said there was a mild slowing of cognitive decline in the high-dose group of one study and no clinical benefit in the other.
But the FDA concluded that the drug’s ability to clear the brain of plaque meant there was a “reasonable likelihood” it would slow the disease. The agency approved the drug based on that “surrogate marker” and directed Biogen to conduct another trial to verify the clinical benefit, with results due in nine years.
The approval of Aduhelm marked the first accelerated approval for an Alzheimer’s drug. The decision sparked a firestorm, in part because a cause-and-effect link between amyloid reduction and a slowing of cognitive decline has not been established.
The steep price for the drug, which is administered intravenously once a month, has sparked fears that it could jeopardize the financial health of Medicare.
The label revision on Thursday was intended to quell some of the controversy enveloping the drug. The new prescribing information clarifies that Aduhelm is recommended for patients with mild cognitive impairment or early-stage dementia from the disease — the population that participated in clinical trials of the drug.
The narrower label limits the recommended population eligible for the drug to 1 million or 2 million Alzheimer’s patients, rather than the more than 6 million people with the disease in the United States, according to biotech analysts.