Washington, DC—
The FDA’s approval of Aduhelm (aducanumab) for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans, was unprecedented in several ways.

Aduhelm is the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease, according to the FDA. It was approved using the accelerated approval pathway, used for drugs that treat serious or life-threatening illnesses and provide a meaningful therapeutic advantage over existing treatments.

In a press release, the FDA explains that accelerated approval “can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients, with a required post-approval trial to verify that the drug provides the expected clinical benefit.”

Controversy about aducanumab, a monthly IV infusion, primarily centered on two issues: its effectiveness in slowing cognitive decline in people with mild memory and thinking issues and the high price.

To address the first issue, the FDA is requiring the company, Biogen, to conduct a new randomized, controlled clinical trial to verify the drug’s benefit. If that fails to occur or the trial doesn’t meet its endpoints, drug regulators can initiate proceedings to withdraw approval of the drug.

As for the second issue, Biogen, its manufacturer, has set the wholesale acquisition cost (WAC) of the drug at $4,312 per infusion for a patient of 74 kg–the average weight of a U.S. patient with mild cognitive impairment (MCI) or mild dementia. The yearly cost at the maintenance dose (10 mg/kg) would be $56,000, although the cost during the first year of treatment would be lower due to the titration period. 

Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, explained why the decision was made in this case, noting, “Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones. Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”

Alzheimer’s is an irreversible, progressive brain disorder that gradually destroys memory and thinking skills and functionality. The specific causes of Alzheimer’s disease are not fully known, but the disease is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections.

In a separate website posting from the FDA’s press release, Dr. Cavazzoni addressed some of the controversy about the approval decision, writing, “We are well-aware of the attention surrounding this approval. We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review. Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. 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.”

He added, “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. We examined the clinical trial findings with a fine-tooth comb, we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, we listened to the perspectives of the patient community, and we reviewed all relevant data. We ultimately decided to use the Accelerated Approval pathway—a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit. In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy.”

That decision was based on three separate studies with total of 3,482 patients. Results indicated that patients receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque, compared with those in the control arms who had no reduction of amyloid beta plaque.

“The need for treatments is urgent: right now, more than 6 million Americans are living with Alzheimer’s disease and this number is expected to grow as the population ages,” Dr. Cavazzoni emphasized.

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