FDA Awards Accelerated Approval to Aducanumab for Alzheimer Disease

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The US Food and Drug Administration (FDA) on Monday approved aducanumab (Aduhelm, Biogen), the first new medication to be approved to treat Alzheimer disease since 2003, according to a press release from the FDA’s Center for Drug Evaluation and Research (CDER).

Notably, aducanumab is the first treatment that targets the pathophysiologic process underlying Alzheimer disease—the presence of amyloid-beta plaques in the brain—vs treating only symptoms of the disease.

Aducanumab received approval under the FDA’s Accelerated Approval Program, a mechanism whereby FDA approves a drug for a serious, life threatening illness for which the novel agent may have therapeutic benefit over existing treatments.

Accelerated approval can be based on “a surrogate or intermediate endpoint that is reasonably likely to predict a clinical benefit to patients” —in this case, reduction in amyloid plaque in the brain serving as a surrogate marker for slowed disease progression.

FDA requires post-approval trials of drugs approved under the accelerated pathway to verify the anticipated benefit. Results of the so-called phase 4 confirmatory trials can trigger FDA regulatory procedures that could lead to removing the drug from the market.

There were 2 phase 3 clinical trials in the late-stage development process for aducanumab. The EMERGE study enrolled 1638 adults aged 50 to 85 years diagnosed with early Alzheimer disease. The high dose of aducanumab met the primary clinical endpoint with a statistically significant reduction of 22% in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score at week 78 vs placebo (P=.01).

The phase 3 ENGAGE study did not replicate EMERGE in terms of change in baseline in CDR-SB score, but a subset of the data was found to support the outcome in EMERGE. Data from the phase 1b PRIME study showed that aducanumab reduced amyloid-beta plaque in the brain in a significant dose-and time dependent fashion. These data also were used to support the accelerated approval.

“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,” wrote CDER director Patrizia Cavazzoni, MD. “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.”

Cavazzoni states that the FDA is confident its decision, based on the “substantial evidence” that the drug reduces amyloid beta plaque and that that outcome is “reasonably likely to predict” the valuable clinical impact aducanumab will have on patients and their loved ones and caregivers.

Aducanumab labeling states the most common adverse reactions reported during clinical trials include amyloid related imaging abnormalities (ARIA)-edema, headache, amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H) microhemorrhage, ARIA-H superficial siderosis, and fall.

Aducanumab is administered via intravenous infusion every 4 weeks, at least 21 days apart.