The “unusual” collaboration, which revived Aduhelm three months after Biogen had canceled clinical trials, unfolded through at least 115 meetings, conversations and e-mail exchanges between the company and the FDA over the course of a year, the report by the Committees on Oversight and reform. and energy and trade.
The joint effort culminated with agency staff helping Biogen prepare a document used to brief the FDA’s advisory committee before it met to discuss Aduhelm on November 6, 2020. Although the FDA often follows an advisory committee’s recommendation, it did not this time. After no members of the advisory committee recommended Aduhelm, the FDA changed course, allowing Biogen to move the drug into an accelerated approval process.
At the FDA’s suggestion, 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 says.
“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 committees’ evaluation, and we continue to consider their findings and recommendations,” the FDA said in a statement responding to the report. “It is the agency’s job to have frequent interactions with companies to ensure we have sufficient information to inform our regulatory decision-making. We will continue to do so, as it is in the best interest of patients. That said, the agency has already begun to implement changes in accordance with the committee’s recommendations.”
The agency had previously conducted an internal investigation into its handling of Aduhelm, concluding more than a year ago that while the cooperation “exceeded the norm in some respects,” there was “no evidence” that the dealings between the company and the regulator “were anything but appropriate.”
The internal report said the decision to work “proactively” with Biogen “is consistent with FDA policy” in light of both the “large unmet medical need” for Alzheimer’s treatment, and an FDA official’s view that one of Aduhelm -the studies can represent “a home run” as far as safety and effectiveness are concerned.
The report by the two House committees also faulted the company, saying Biogen knew the original price of $56,000 per year — reduced to $28,000 in January 2022 — would place a heavy burden on patients. But the Cambridge, Mass.-based company estimated the treatment could earn Biogen as much as $18 billion a year and cheered in a slide presentation to the board: “Our ambition is to make history” and “establish [the drug] as one of the best pharmaceutical launches of all time.”
In fact, Aduhelm turned out to be a financial dud, generating $3 million in revenue for all of 2021.
In a statement responding to the report, Biogen said it had cooperated with the committees and “stands by 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 improper relations between the agency and the company.
Biogen stuck to the initial $56,000-a-year price tag despite estimates that the drug could end up costing Medicare up to $12 billion in a single year. Other Alzheimer’s treatments are sold for much less. A year’s supply of Aricept costs less than $8,000; Exelon, 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 lays out 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 up to the FDA and the company to change their policies, it’s unclear whether they will actually prevent future episodes like this from occurring.
The committees recommended that the FDA document all communications with drug sponsors, establish a system for working with companies to produce the reports used to inform its own advisory committees, and update its formal guidance for the development and review of new Alzheimer’s drugs.
Drug sponsors, the committees recommended, should be open and transparent when expressing to the FDA any concerns about the safety and effectiveness of treatments, as well as consider the opinions of outside experts when setting prices for new drugs.
Aduhelm, a lab-made protein administered directly into a patient’s vein, was said to work by reducing a sticky substance in the brain called amyloid beta, which clumps between neurons and disrupts their function. Some researchers have theorized that the accumulation of amyloid beta 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 trials after receiving an independent report that concluded the treatment was unlikely to slow the memory loss, confusion and other symptoms of brain failure caused by Alzheimer’s disease.
But the drug’s death was short-lived.
The report shows that two months after the trials ended, representatives from Biogen and the FDA met at a neurology conference in Philadelphia and discussed findings from the studies. The FDA official suggested the agency and the company schedule a special meeting to discuss data from the trials.
FDA documents reviewed in the new report show that Biogen began informal talks with the agency to assess whether data from the unfinished studies showed any benefits for patients. A meeting between the FDA and Biogen in mid-June 2019 led to both agreeing to form a joint “working group”.
The collaboration will see the FDA and Biogen move forward with the drug, although employees at both the agency and the company expressed reservations about some of the decisions made.
For example, the FDA issued accelerated approval for Aduhelm despite not receiving the support of a single member of its own advisory committee, and without putting the idea up for discussion by any internal or external body.
In addition, the FDA’s approval was at odds with its own guidelines for the early treatment of Alzheimer’s disease, which stated that “there is no sufficiently reliable evidence” that a drug’s effect on amyloid beta by itself would be enough to benefit patients. Scientists have expressed conflicting opinions about whether amyloid beta is a cause of Alzheimer’s or just a consequence of the disease.
The report also found that a team of Biogen employees examined the financial impact the starting price of Aduhelm would have on patients and concluded that the country’s “over 65 population 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 incomes of less than $50,000 a year and more than one-third have assets worth less than 5 000 dollars. .
Although the report found that the company “appears to have developed financial assistance programs for eligible patients,” investigators wrote that “these programs would leave significant gaps in coverage.”
Despite the anticipated hardship the price would cause patients, Biogen expected to spend “between $500 million and $600 million to build out the sales force” to market the drug, the report said.
Five months after the drug hit the market, the Centers for Medicare and Medicaid Services announced that monthly premiums for Medicare Part B would rise 14.5 percent in 2022, half of that in anticipation of higher costs due to the new Alzheimer’s treatment .
The report said the percentage increase translated into a $21.60 jump in monthly premiums for Medicare Part B beneficiaries, “reportedly the largest dollar increase in the program’s history.”
For its part, Biogen went ahead with a broad label that Aduhelm was for “people with Alzheimer’s disease”, despite the reservations of the staff about the lack of evidence of clinical benefit for patients in more advanced stages of the disease than those involved in the clinical trials. Some at the company even expressed concern that continuing with the branding plan “could damage the company’s credibility,” the report said.