The “unusual” collaboration, which Aduhelm revived three months after Biogen canceled clinical trials, unfolded through at least 115 meetings, phone calls and email exchanges between the company and the FDA in a year, the Committees’ report said. on Oversight and Reform. and Energy and Trade.
The collaborative effort came to a head when Biogen agency staff helped draft a document used to brief the FDA’s advisory committee before it met on Nov. 6, 2020, to discuss Aduhelm. While the FDA often follows an advisory committee’s recommendation, this time it didn’t. After no member of the advisory committee recommended Aduhelm, the FDA changed course, allowing Biogen to move its drug into an expedited approval process.
At the suggestion of the FDA, the drug was labeled for use by the country’s more than 6 million Alzheimer’s patients, even though it had only been tested on people with early Alzheimer’s and mild symptoms, the report said.
“It’s the worst decision the FDA has ever made” in the past half century, said Sidney Wolfe, founder of the advocacy group Public Citizen’s Health Research Group. “It was an unprecedented alliance between the company and the FDA.”
“We cooperated fully with the evaluation of the committees and we continue to review their findings and recommendations,” the FDA said in a statement in response to the report. “It is the agency’s job to interact with companies on a regular basis to ensure we have enough information to inform our regulatory decision-making. We will continue to do this because it is in the best interest of the patient. That said, the agency has already begun implementing changes consistent with the committee’s recommendations.”
The agency had previously conducted an internal investigation into Aduhelm’s handling and concluded more than a year ago that while the collaboration “exceeded the norm in some respects”, there was “no evidence” that dealings between the company and the regulator were “anything but appropriate.”
The internal report said the decision to “proactively collaborate” with Biogen is “consistent with FDA policy” in light of both “the high unmet medical need” for Alzheimer’s treatment, and the opinion of an FDA official that one of the Aduhelm studies “hit a home run” in terms of safety and effectiveness.
The two House committees’ report also berated the company, saying Biogen knew the initial price of $56,000 a year — reduced to $28,000 by January 2022 — would be a heavy burden on patients. But the Cambridge, Massachusetts-based company estimated that the treatment could bring Biogen as much as $18 billion a year and delighted in a slide presentation to the board: “Our ambition is to make history” and ” [the drug] as one of the best pharma launches of all time.”
In fact, Aduhelm turned out to be a financial dud, generating $3 million in revenue for all of 2021.
Commenting on the report, Biogen said it had cooperated with the committees and “upholds the integrity of the actions we have taken.” Biogen’s statement also cited the FDA’s internal investigation, which concluded there was no evidence of impropriety in dealings between the agency and the company.
Biogen stuck with its initial price tag of $56,000 a year, despite projections that the drug could cost Medicare up to $12 billion in a year. Other treatments for Alzheimer’s disease sell for much less. A year’s supply of Aricept costs less than $8,000; Excelon, a drug in the same family, costs about $8,800 for a year’s supply; and Namenda costs less than $3,000 per year.
The report includes recommendations that the FDA should follow to “help restore the confidence of the American people,” as well as actions that Biogen and other drug companies should take to “fulfill their responsibilities to patients and families.” Since the recommendations leave it to the FDA and company to change their policies, it’s unclear if they will actually prevent future episodes like this.
The committees recommended that the FDA document all of its communications with drug sponsors, establish a system for partnering with companies to produce the reports used to inform its own advisory committees, and review its formal guidelines for developing and assessing new Alzheimer’s disease. updating medications.
Drug sponsors, the committees recommended, should be open and clear in expressing any concerns about the safety and effectiveness of treatments to the FDA, as well as considering outside expert opinions when setting prices for new drugs.
Aduhelm, a lab-made protein administered directly into a patient’s vein, is said to work by reducing a sticky substance in the brain called amyloid beta, which clumps between neurons and interferes with their function. Some scientists have theorized that beta-amyloid buildup in the brain causes Alzheimer’s disease.
In September 2015, Biogen began enrolling patients in two Phase 3 clinical trials, which test the safety and effectiveness of a drug and compare it to standard treatment. Three and a half years later, in March 2019, the company announced it was ending both studies after receiving an independent report that concluded that the treatment was unlikely to reverse the memory loss, confusion and other symptoms of brain damage caused by Alzheimer’s disease. to slow down.
But the drug’s death was short-lived.
The report shows that two months after the studies ended, representatives from Biogen and the FDA met at a neurology conference in Philadelphia and discussed the findings of the studies. The FDA official suggested that the agency and company schedule a special meeting to discuss the data from the trials.
FDA documents reviewed in the new report show that Biogen has begun informal discussions with the agency to assess whether data from the unfinished studies revealed any benefit to patients. A meeting between the FDA and Biogen in mid-June 2019 led to both agreeing to form a joint “working group.”
The collaboration would see the FDA and Biogen move forward on the drug, though staff at both the agency and the company expressed reservations about some of the decisions made.
For example, the FDA gave accelerated approval to Aduhelm, despite not receiving support from a single member of its own advisory committee and without questioning the idea by any internal or external body.
In addition, the FDA’s approval went against its own early treatment guidelines for Alzheimer’s disease, which stated that “there is not enough reliable evidence” that a drug’s effect on amyloid beta would be sufficient on its own to benefit patients. to come. Scientists have expressed conflicting opinions about whether beta-amyloid is a cause of Alzheimer’s disease or simply a consequence of the disease.
The report also found that a team of Biogen employees examined the financial impact that Aduhelm’s initial price would have on patients and concluded that the nation’s “over-65s will face challenges with [their] ability to pay.” The team estimated that two-thirds of Medicare patients at risk of developing Alzheimer’s would have to pay some of the costs themselves, even though more than half have an income of less than $50,000. per year and more than a third have assets worth less than $5,000.
While the report found that the company “appears to have developed financial assistance programs for eligible patients,” the researchers wrote that “these programs would leave significant gaps in coverage.”
Despite the expected hardship the price would impose on patients, Biogen expected to spend “between $500 million and $600 million to build out its sales team” to bring the drug to market, the report said.
Five months after the drug hit the market, the Centers for Medicare and Medicaid Services announced that the monthly premium for Medicare Part B would increase 14.5 percent in 2022, half of that in anticipation of higher costs from the new treatment from Alzheimer’s.
The report said the percentage increase translated into a $21.60 increase in monthly premiums for Medicare Part B beneficiaries, “reportedly the largest dollar increase in program history.”
Biogen, for its part, continued with a broad label that Aduhelm was for “people with Alzheimer’s disease,” despite staff’s concerns about the lack of evidence of clinical benefit for patients in more advanced stages of the disease than those involved. are in clinical trials. In fact, some within the company were concerned that continuing with the labeling plan “could damage the company’s credibility,” the report said.