The Food and Drug Administration failed to follow its own protocol in a 2021 decision to approve the Alzheimer’s disease drug aducanumab (Brand name: Aduhelm), a U.S. House investigation has revealed. The news precedes an expected Jan. 6 decision on lecanemab, an Alzheimer’s drug in the same anti-amyloid class and involving the same maker.

The report, released Dec. 29, called drugmaker Biogen’s launch plans of Aduhelm “aggressive,” its pricing too high and the FDA’s decision to approve it unorthodox. In a key clinical finding, investigators criticized the FDA’s broad label indication for Aduhelm and Biogen’s acceptance of that label, “despite a lack of clinical data on all Alzheimer’s disease stages and Biogen’s reservations.”

“This report documents the atypical FDA review process and corporate greed that preceded FDA’s controversial decision to grant accelerated approval to Aduhelm,” Frank Pallone, Jr. (D-NJ), chairman of the Energy and Commerce Committee, said in a statement.

New drug decision in the wings

Like Aduhelm, lecanemab targets anti-amyloid plaques in the brain, a hallmark of Alzheimer’s disease. Both drugs are monoclonal antibodies that must be infused. Each has been linked to brain bleeds in a small percentage of trial participants and each requires regular brain scans to watch for signs of such problems. Deaths potentially related to these side effects have also been reported.

With demand growing for dementia treatments and more anti-amyloid antibody drugs in the pipeline, “it is crucial that FDA and drug companies adhere to established procedures and conduct themselves with the transparency necessary to earn public trust,” Pallone said. The findings should be “a wake-up call” for FDA reform and a call to action for congressional oversight of the pharmaceutical industry “to ensure they don’t put profits over patients,” he added.

House investigators, including the Oversight and Reform Committee, recommended that the FDA take “swift action” to ensure that future reviews of Alzheimer’s disease treatments do not lead to the same doubts about its integrity.

Biogen, currently looking for approval of lecanemab along with partner Eisai, “must provide more transparency into its pricing and analyses of clinical benefit to ensure that new drugs are effective and available for those who need them,” the report concluded.

Aduhelm skepticism

The FDA greenlit Aduhelm in June 2021 under a cloud of controversy, with some FDA advisers resigning in protest during the process. Various experts initially stacked up against the drug, including some leading long-term care experts who called for further evidence of its safety and efficacy before use in elderly patients. In an effort to mitigate concerns, the FDA’s approval required Biogen to conduct and report on further clinical trials.

In April 2022, Medicare decided to cover the high cost of treatment with Aduhelm only for highly qualified participants in approved clinical trials. The move to severely restrict drug coverage in this way was unusual, but appropriate for the Medicare population, officials with the Centers for Medicare & Medicare Services said at the time.

Biogen expected Aduhelm to be a burden to patients and Medicare, yet planned to spend billions to market the drug, the current report found. Its initial price of $56,000 per year was set “unjustifiably high,” with a goal to “make history” for the company, despite these projected impacts, investigators said. 

Coverage limits

Patients’ advocates, meanwhile, have been critical of the coverage and use restrictions associated with Aduhelm. As the expected approval decision for lecanemab nears, there is a push to ensure that more patients with Alzheimer’s can access anti-amyloid antibody drugs, despite their relative newness and questions surrounding their safety.

The Alzheimer’s Association, for example, in December asked CMS to provide full coverage of FDA-approved dementia drugs. The organization pointed to a growing consensus in the scientific and medical communities about the clinical benefits of amyloid removal from the brains of those living with mild cognitive impairment and early-stage Alzheimer’s disease. It also cited new clinical data demonstrating benefits from lecanemab.

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