June 9, 2021
On June 7, the U.S. Food and Drug Administration approved the use of the experimental drug aducanumab for patient treatment during the early phases of Alzheimer’s disease—overriding the conclusion of an FDA advisory committee last year that there was not enough evidence to support the effectiveness of the treatment.
The FDA has not approved a novel therapy for Alzheimer’s disease since 2003.
The FDA approved aducanumab, also known as Aduhelm, using its “accelerated approval” program, which allows for the earlier approval of a drug for a serious or life-threatening illness even though more study into the drug’s benefits may be needed.
“There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives,” Dr. Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said in Monday’s announcement.
“At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward,” she said, noting that the FDA ultimately decided to use accelerated approval and “concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.”
“FDA will continue to monitor Aduhelm as it reaches the market and ultimately the patient’s bedside,” Cavazzoni said.
In November, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was asked to vote on several questions about evidence of the drug’s effectiveness. In response to a question about whether it was reasonable to consider data from one positive study as the primary evidence of aducanumab’s effectiveness for the treatment of early Alzheimer’s disease, none of the committee members voted yes; ten voted no and one was uncertain.
The committee’s opinions were then left with the FDA as the agency mulled whether to approve the drug or pump the brakes.
“In all studies in which it was evaluated, however, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Cavazzoni said on Monday. “It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline.”
The pharmaceutical company Biogen and its Japanese partner Eisai developed aducanumab—administered through intravenous infusion to treat early Alzheimer’s disease. The drug was developed for patients with mild cognitive impairment, not severe dementia.
Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian in New York, who had patients in the original aducanumab clinical studies, told CNN the drug targets the earliest symptomatic phase of the disease, called mild cognitive impairment due to Alzheimer’s. Treatment of the pre-dementia period was the focus of the FDA’s decision.
“We have to really temper expectations and explain to people that this drug is meant for the earliest symptomatic phases,” he said. “It pains me to say this, but if I have a severe Alzheimer’s patient that can no longer speak or interact much with others and their family member is begging me to give them this drug, I won’t be able to do it.”
Some groups, including the nonprofit Public Citizen’s Health Research Group, argued that the FDA should not approve aducanumab for treatment of Alzheimer’s disease due to lack of evidence of its effectiveness.
There have also been concerns around cost: Biogen announced on Monday that the wholesale cost of treatment with aducanumab—which requires an infusion once every four weeks—is about $4,312 per infusion, making the annual cost around $56,000 for a high dose.
However, the participating companies said, “Biogen and Eisai are committed to providing access to ADUHELM for patients across a spectrum of financial situations,” the company noted in its announcement. “For qualified, commercially insured ADUHELM patients, co-pay and infusion cost assistance programs may reduce out-of-pocket costs to as low as $0. Patients who are covered by Medicare through a Medicare Advantage plan have a maximum annual out-of-pocket cap.”
In May, the Institute for Clinical and Economic Review released a draft report estimating that the drug should cost between $2,560 to $8,290 per year, and noted that “the evidence is insufficient to conclude that the clinical benefits of aducanumab outweigh its harms or, indeed, that it reduces progression” of Alzheimer’s disease.
Other organizations, such as the Alzheimer’s Association, have supported approval of the drug.
“This approval is a victory for people living with Alzheimer’s and their families,” Harry Johns, the association’s president and CEO, said in a post on Twitter on Monday.
Research contact: @CNN