The “unusual” collaboration, which resurrected Aduhelm three months after Biogen canceled clinical trials, unfolded through at least 115 meetings, calls and email exchanges between the company and the FDA in one year, according to the Report of the Oversight and Reform Committees, and Energy and Commerce.
The joint effort culminated with agency staff helping Biogen draft a document used to brief the FDA Advisory Committee before it meets to discuss Aduhelm on November 6, 2020. Although the FDA is following often the recommendation of an advisory committee, it did not this time. After no member of the advisory committee recommended Aduhelm, the FDA changed course, allowing Biogen to move its drug through an accelerated approval process.
At the FDA’s suggestion, the drug was labeled for use by more than 6 million Alzheimer’s patients nationwide, even though it had only been tested on people with the disease. early Alzheimer’s and mild symptoms, according to the report.
“This is the worst decision the FDA has ever made” in the past half-century, said Sidney Wolfe, founder of 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 continue to review their findings and recommendations,” the FDA said in a statement responding to the report. “It is the agency’s job to interact frequently with companies to ensure that we have adequate information to inform our regulatory decision-making. We will continue to do so because it is in the best interests of patients. That said, the agency has already begun to implement changes consistent 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 although the collaboration “went above the norm in some respects”, there was “no evidence” that the relationship between the company and the regulator “was anything but appropriate.”
The internal report says the decision to work “proactively” with Biogen “is consistent with FDA policy” in light of both the “significant unmet medical need” for the treatment of Alzheimer’s disease and the opinion of an FDA official that one of Aduhelm’s studies may represent a “home run” in regards to safety and efficacy.
The report from both House committees also blamed the company, saying Biogen knew the original price of $56,000 a 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 bring Biogen up to $18 billion a year and gloated in a slide presentation to its board: “Our ambition is to make history” and “to establish [the drug] as one of the best pharma launches of all time.
In fact, Aduhelm turned out to be a financial misfire, generating $3 million in revenue for all of 2021.
In a statement responding to the report, Biogen said it 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 impropriety in the agency’s relationship with the company.
Biogen stuck with the original price of $56,000 per year despite projections that the drug could cost Medicare up to $12 billion in a single year. Other treatments for Alzheimer’s disease sell for much less. One year supply of Aricept costs less than $8,000; Exelon, a drug from the same family, costs about $8,800 for a one-year supply; and Namenda costs less than $3,000 per year.
The report sets out recommendations the FDA should follow to “help restore the trust of the American people,” as well as steps Biogen and other pharmaceutical companies should take to “fulfil their responsibility to patients and families.” “. Since the recommendations leave it up to the FDA and the company to change their policies, it’s unclear if they will actually prevent future episodes like this from happening.
The committees recommended that the FDA document all of its communications with drug sponsors, establish a system of partnering with companies to produce the reports used to inform its own advisory committees, and update its official guidelines for development and review. new drugs for Alzheimer’s disease.
Drug sponsors, the committees recommended, should be open and clear in raising any concerns about the safety and efficacy of treatments with the FDA, as well as considering the opinions of outside experts when setting prices. new drugs.
Aduhelm, a lab-made protein given directly into a patient’s vein, is believed to work by reducing a sticky substance in the brain called beta-amyloid, which clumps between neurons and disrupts their function. Some scientists have speculated that the buildup of beta-amyloid in the brain causes Alzheimer’s disease.
In September 2015, Biogen began enrolling patients in two Phase 3 clinical trials, which test a drug’s safety and effectiveness and compare it to a standard treatment. Three and a half years later, in March 2019, the company announced that it was ending both trials after receiving an independent report concluding that the treatment was not likely to slow memory loss, confusion and other symptoms of brain impairment caused by Alzheimer’s disease.
But the drug’s death was short-lived.
The report shows that two months after the trials were completed, representatives from Biogen and the FDA met at a neurology conference in Philadelphia and discussed the study results. The FDA official suggested the agency and the company schedule a special meeting to discuss the trial data.
FDA documents reviewed in the new report show that Biogen has begun informal talks with the agency to consider whether data from the unfinished trials revealed benefits for patients. A meeting between the FDA and Biogen in mid-June 2019 led to the two agreeing to form a joint “task force.”
The collaboration would lead the FDA and Biogen to move forward on the drug, although agency and company staff have expressed reservations about some of the decisions that have been made.
For example, the FDA issued fast-track approval for Aduhelm despite not having the support of a single member of its own advisory committee, and without submitting the idea for discussion by any internal or external body.
Moreover, the FDA’s approval went against its own guidelines for early treatments for Alzheimer’s disease, which stated that “there is not sufficiently reliable evidence” that the effect of drug on beta-amyloid alone would be enough to benefit patients. Scientists have expressed conflicting opinions as to whether beta-amyloid is a cause of Alzheimer’s disease or simply a consequence of the disease.
The report also revealed that a team of Biogen employees reviewed the financial impact that the initial 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 below $50,000. dollars a year and more than a third have assets worth less than $5,000.
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 expected hardship the price would impose on patients, Biogen expected to spend “between $500 million and $600 million to bolster its sales force” to bring the drug to market, according to the report.
Five months after the drug entered the market, the Centers for Medicare and Medicaid Services announced that the monthly premium for Medicare Part B would increase by 14.5% in 2022, half of it in anticipation of rising costs due to the new treatment for Alzheimer’s disease.
The report says the percentage increase translated into a $21.60 increase in monthly premiums for Medicare Part B beneficiaries, “which would be 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 staff reservations about the lack of evidence of clinical benefit for patients. at more advanced stages of the disease than those involved in the clinical trials. Some within the company even expressed concern that continuing with the labeling plan “could damage the credibility of the company”, according to the report.