On Monday, June 7, 2021, The FDA approved the use of the experimental drug aducanumab for the early phases of Alzheimer’s disease — despite an FDA advisory committee concluding last year that there is not enough evidence to support the effectiveness of the treatment.
The drug was developed for patients with mild cognitive impairment, not severe dementia, and intended to slow the progression of Alzheimer’s disease — not just ease symptoms.
The FDA has not approved a new Alzheimer’s drug in nearly 20 years.
In November, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was asked to vote on several questions about the 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 — 10 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.
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.
“This drug targets the earliest symptomatic phase of the disease, called mild cognitive impairment due to Alzheimer’s. Treatment of this pre-dementia period is what the FDA is deciding on,” 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 said.
“We have to really temper expectations and explain to people that this drug is meant for the earliest symptomatic phases,” he added. “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.”
Aducanumab’s road to seeking FDA approval has been rocky — and controversial.
In March 2019, Phase 3 clinical trials of aducanumab were discontinued because a futility analysis found the trials were unlikely to meet their primary goals at completion.
“The futility analyses showed the studies were most likely to fail,” said Isaacson of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian.
Several months later, Biogen announced that a new analysis, which included more patients, showed that those who received high doses of aducanumab experienced a reduction in clinical decline in one trial.
The company noted in FDA briefing documents last year that patients treated with high-dose aducanumab showed 22% less clinical decline in their cognitive health at about 18 months — meaning the progression of their early Alzheimer’s disease slowed — compared with those who received a placebo
Results for some patients in another study supported those findings, as well.
“Now the messaging was like, ‘Wait a minute. It worked, and it especially works if you pull all the high dosages from the two studies,'” Isaacson said. “Because it would take years to repeat a study, and considering the lack of available therapies to treat the pre-dementia phase, the company made an uncharacteristic decision — to still apply to the FDA.”
In July 2020, Biogen completed its submission to the FDA for a Biologics License Application for approval of the drug.
Since then, Alzheimer’s disease researchers, doctors, and patients have been waiting for the FDA’s decision.
Some groups, including the nonprofit Public Citizen’s Health Research Group, argued that the FDA should not approve aducanumab for the treatment of Alzheimer’s disease due to a lack of evidence of its effectiveness.
In April, the nonprofit wrote a letter to Secretary of Health and Human Services Xavier Becerra asking the department’s Office of
Inspector General to investigate the “close collaboration” between FDA and Biogen regarding the company’s application for approval of aducanumab.
There have also been concerns around cost.
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 — not up to $50,000 based on market analyst estimates — 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.
On Friday, the Alzheimer’s Association’s website said, “Whatever the final decision by the FDA, this is an important moment. We have never before been this close to the approval of a medication for Alzheimer’s that could change the progression of the disease, not just the symptoms. Together, we can continue working toward our vision of a world without Alzheimer’s and all other dementia.”
There has been so much attention around the drug that Washington University’s Knight Alzheimer Disease Research Center in St. Louis issued a statement on Friday noting that if the drug is approved, “it will still likely take several months for the medication to pass other regulatory steps and become available to patients.”