First New Treatment Approved for Alzheimer Disease in Nearly 2 Decades

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Today, the US Food and Drug Administration (FDA) approved Biogen’s anti-amyloid, disease-modifying agent aducanumab for the treatment of Alzheimer disease. Aducanumab represents a first-of-its-kind treatment, as it targets the fundamental pathophysiology of the disease. It is also the first new treatment approved for Alzheimer disease since 2003.¹

“Alzheimer 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,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research. “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.”¹

Researchers evaluated aducanumab’s efficacy in 3 separate double-blind, randomized, placebo-controlled dose-ranging studies, studying a total of 3482 participants with Alzheimer disease. Patients receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while patients receiving the control had no reduction of amyloid beta plaque.

The FDA noted that in all the studies in which aducanumab was evaluated, data suggested it “consistently and very convincingly” reduced amyloid plaques in both a dose- and time-dependent fashion. This may result in a reduction in clinical decline.²

This approval follows intense debate within the medical community—patient groups pushed for approval while experts recommended caution.³ An FDA independent advisory committee voted against approval in November 2020,⁴ stating that data did not demonstrate aducanumab slowed cognitive decline.

Under the accelerated approval provisions, the FDA is requiring Biogen to conduct a new randomized, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may withdraw approval of the drug.

Stephen Salloway, MD, MS, a principal investigator and director of Neurology and the Memory and Aging Program at Butler Hospital, said this approval “would just be the beginning; a stepping stone. Rather than the final breakthrough, it would be the first. To quote a colleague of mine, ‘in order to get the best-in-class drug, we must have the first-in-class drug.’ That's how I see this.”²

At the 2021 American Academy of Neurology (AAN) Annual Meeting in April, Biogen presented details of a phase 3b redosing trial of aducanumab. The trial, EMBARK (NCT04241068), will be an open-label, single-arm clinical safety study with a 24-month treatment period, evaluating long-term safety and efficacy of aducanumab in participants with Alzheimer disease. Participants will receive 10-mg/kg aducanumab via intravenous infusion every 4 weeks. Primary endpoints include the following: the number of participants with adverse events, serious adverse events, adverse events s leading to treatment discontinuation or study withdrawal, amyloid-related imaging abnormality-edema (ARIA) or amyloid-related imaging abnormality-hemorrhage or superficial siderosis, and the number of participants with anti-aducanumab antibodies.

Helen Lavretsky, MD, MS, in an exclusive quote to Psychiatric Times^TM said, "As the first approved AD medication in nearly 20 years, this is ​big n​ews and will change our clinical practice considerably. It provides new hope to our community of patients, their caregivers and healthcare providers."

Dr Lavretsky also had some clinical considerations she found were important to note:

1. The trials included amyloid-positive MCI/mild AD patients with MMSE cutoff of 24.

2. Amyloid-related imaging abnormalities (ARIA) occurred in 40% on the higher dose and was more common in ApoE4 carriers.

3. General prescribing guidelines:

-Infusions start at a low dose and increase every 2 months until reaching the high dose of 10 mg/kg.

-At a minimum, patients should have a brain MRI within the year before starting the drug and should obtain additional MRIs before the 7th and 12th monthly doses.

-The most common adverse reactions include brain swelling, headache, brain microbleeds and fall.

References

1. US Food and Drug Administration. FDA grants accelerated approval for Alzheimer’s drug. June 7, 2021. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug

2. Hoffman M. Aducanumab approved for Alzheimer disease treatment. NeurologyLive. June 7, 2021. https://www.neurologylive.com/view/aducanumab-biogen-approved-alzheimer-disease-modifying-treatment

3. Belluck P, Robbins R. Alzheimer’s drug poses a dilemma for the FDA. The New York Times. June 5, 2021. https://www.nytimes.com/2021/06/05/health/alzheimers-aducanumab-fda.html

4. Hoffman M. Aducanumab approval not recommended by FDA advisory committee. NeurologyLive. November 6, 2020. https://www.neurologylive.com/view/aducanumab-approval-not-recommended-by-fda-advisory-committee