House investigation faults FDA, Biogen for Alzheimer’s drug approval

The “unusual” collaboration, which resurrected Aduhelm three months after Biogen had canceled clinical trials, unfolded through at least 115 meetings, calls and email exchanges between the company and the FDA in a year, said the report by the Committees on Oversight and Reform, and Energy and Commerce.

The joint effort climaxed with staff from the agency helping Biogen draft a document used to brief the FDA’s advisory committee before it met to discuss Aduhelm on Nov. 6, 2020. Although the FDA often follows an advisory committee’s recommendation, it did not this time. After no member of the advisory committee recommended Aduhelm, the FDA changed course, allowing Biogen to move its drug to an accelerated approval process.

At the FDA’s suggestion, the drug was labeled for use by the nation’s more than 6 million Alzheimer’s patients, even though it had been tested only 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 fully cooperated with the Committees’ evaluation and we continue to review their findings and recommendations,” the FDA said in a statement responding to the report. “It is the agency’s job to frequently interact with companies in order to ensure that we have adequate 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 started implementing changes consistent with the Committee’s recommendations.”

The agency had previously conducted an internal investigation of its handling of Aduhelm, concluding more than a year ago that although the collaboration “exceeded the norm in some respects,” there was “no evidence” that dealings between the company and 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 the Aduhelm studies could represent “a home run” as far as safety and effectiveness.

The report by the two House committees faulted the company, too, saying that Biogen knew the initial $56,000-per-year price ― reduced to $28,000 in January 2022 ― would put a heavy burden on patients. But the Cambridge, Mass.-based company estimated the treatment could earn Biogen as much as $18 billion per year and exulted in a slide presentation to its board: “Our ambition is to make history” and “establish [the drug] as one of the top pharmaceutical launches of all time.”

In fact, Aduhelm proved 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 that there was no evidence of impropriety in the dealings between the agency and company.

Biogen stuck with the initial $56,000-per-year price tag despite projections that the drug could wind up costing Medicare up to $12 billion in a single year. Other Alzheimer’s treatments sell 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 American people’s trust,” as well as measures that Biogen and other drug companies should take to “fulfill their responsibility to the patients and families.” Since the recommendations leave it to the FDA and company to change their policies, it is unclear whether they will actually prevent future episodes like this from occurring.

The committees recommended that the FDA document all its communications with drug sponsors, establish a system for partnering with companies to produce the reports used to brief its own advisory committees, and update its formal guidance for developing and reviewing new Alzheimer’s drugs.

Drug sponsors, the committees recommended, should be open and clear in spelling out to the FDA any concerns about the safety and effectiveness of treatments, as well as consider opinions from outside experts when setting prices for new medications.

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 scientists have theorized that buildup 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 with standard treatment. Three and a half years later, in March 2019, the company announced it was ending both trials after receiving an independent report concluding that the treatment was not likely to slow the 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 ceased, 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 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 review whether data from the unfinished trials revealed some 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 lead to the FDA and Biogen moving forward on the drug, even though staff at both the agency and the company expressed reservations about some of the decisions that were made.

For example, the FDA issued accelerated approval for Aduhelm despite failing to gain 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 ran counter to its own guidelines on early Alzheimer’s disease treatments, which said 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 as to whether amyloid beta is a cause of Alzheimer’s or simply a consequence of the disease.

The report also found that a team of Biogen staff examined the financial impact 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 cost 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.

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 build out its sales force” to market the drug, the report said.

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 rise by 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 to 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 from 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 inside the company even expressed concern that pushing ahead with the labeling plan “could damage the company’s credibility,” the report said.