Insights into FDA’s decision to approve Biogen’s Aduhelm

By Jane Byrne contact

- Last updated on GMT

© GettyImages/Waldemarus
© GettyImages/Waldemarus

Related tags: Aducanumab, Biogen, Fda, Alzheimer's disease

Statisticians at the US Food and Drug Administration (FDA) said there was insufficient evidence to support the agency’s approval of the Alzheimer’s drug produced by Biogen, according to newly released internal memos.

The US agency approved​ Biogen’s Aduhelm (aducanumab) for the treatment of Alzheimer’s on June 7: making it the first new treatment approved for the disease since 2003.

Communications published yesterday​ [June 22] showed that the FDA’s drug statistics office found there was a lack of sufficient clinical trial data to put Biogen’s product on the market.

However, the internal memos showed more senior officials decided that the evidence indicating that the drug worked, while inconclusive, supported accelerated approval (AA) of aducanumab for the treatment of patients with Alzheimer’s disease (AD).

Peter Stein, director of the FDA’s office of new drugs, in a memo detailing his support for the AA approach for Aduhelm, said he agreed with the agency’s Office of Neuroscience that the data was “not sufficiently compelling or persuasive to meet the substantial evidence standard for standard approval.”

Nonetheless, he said studies strongly suggest that treatment with aducanumab may result in clinical benefit.

“FDA, then, is faced with a situation where the available evidence on the clinical endpoints is short of what we would require for standard approval of aducanumab.

“At the same time, patients with [Alzheimer’s] have a serious, progressive, ultimately fatal disease and are desperate for treatments.”

The drugs approved for AD provide some symptomatic benefit, but do not have the potential to alter the underlying pathology of disease and thereby alter disease progression, as does aducanumab, he noted.

FDA has the statutory authority to approve drugs using AA; the current situation with aducanumab fits well into this approach which was, in fact, intended to support approval at a time when the drug has been demonstrated to be effective with respect to certain endpoints but when there remains residual uncertainty regarding clinical benefit.

“The effect of the drug in reducing amyloid plaque was established in the Phase 3 trials, supported by the Phase 2 study. Thus, there is substantial evidence that aducanumab reduces amyloid plaque.”

Under the accelerated approval pathway, Biogen must conduct a new clinical trial to verify the drug’s clinical benefit.

Worst drug approval decision in recent US history’

The FDA is facing criticism from many quarters over the approval, hence the rationale behind making such internal deliberations public.

Earlier this month, three members of a US FDA advisory committee resigned in protest after the agency went ahead and approved the Biogen drug despite their reservations about its efficacy.

In November 2020, that group of external experts, the Peripheral and Central Nervous System Drugs Advisory Committee, voted against recommending the drug.

A BMJ story revealed that one of those who resigned, Harvard professor of medicine, Aaron Kesselheim, wrote in a letter to acting FDA commissioner, Janet Woodcock, that the approval of Biogen’s drug was “probably the worst drug approval decision in recent US history.”

Also resigning over the FDA move were Mayo Clinic neurologist, David Knopman, and Washington University neurologist, Joel Perlmutter.

Huge patient interest in drug

Maria C Carrillo, Alzheimer’s Association chief science officer, told BioPharma-Reporter, following the controversial FDA decision, that the approval of aducanumab is of huge interest to patients ​and their families.

"This is the first FDA-approved treatment that slows decline due to Alzheimer’s disease. This means individuals may have more time to actively participate in daily life, have sustained independence and hold on to memories longer. Aducanumab addresses Alzheimer’s in a new way compared to currently approved drugs. This therapy slows progression of the disease, rather than only addressing symptoms.

"It is the first approved therapy of this type; it demonstrates that removing amyloid from the brain can delay cognitive and functional decline in people living with Alzheimer’s.”

Eliminating barriers to access is the organization's highest priority. At the moment, it is difficult to tell how long it will take for a sizeable number of patients to access the treatment. 

“But we anticipate that demand will be high,” ​said Carrillo. 

Millions of people may be eligible for this therapy, and our direct experience with our constituents tells us that they are enthusiastic about the chance to have access to new therapies.

"We know that infusion therapies have been made available under Medicare and insurance for conditions like cancer and multiple sclerosis, so it is reasonable to expect this for aducanumab.”

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