Donanemab for Alzheimer’s Gets Unanimous Thumbs Up From FDA Panel

An 11-member advisory panel to the US Food and Drug Administration (FDA) has unanimously concluded that the investigational anti-amyloid donanemab is effective for the treatment of patients with early symptomatic Alzheimer’s disease (AD) and that the potential benefits outweigh the risks in this patient population. The June 10 meeting of the Peripheral and Central Nervous System Drugs Advisory Committee was convened specifically to advise the FDA on the safety and efficacy of the drug based on results of the TRAILBLAZER-ALZ 2 trial.

As previously reported by Medscape Medical News, donanemab significantly reduced brain amyloid plaque burden and significantly slowed cognitive and functional decline compared with placebo.

After a comprehensive review of the data, the advisory committee voted 11 to 0 in favor of Eli Lily’s donanemab for treatment of early symptomatic AD (mild cognitive impairment or mild dementia).

Convincing Efficacy, Manageable Risks

The general consensus from the panel was that donanemab showed “convincing” efficacy with “acceptable and manageable” risks, including the risk for amyloid-related imaging abnormalities (ARIA), said Committee Chairperson Thomas Montine, MD, PhD, with Stanford University in California.

If donanemab is approved, it will be “important to minimize risk of ARIA with careful MRI monitoring and to have detailed discussions with patients and care partners regarding individual risk-benefit and allow patients and their care partners to make informed decisions for themselves and their loved ones,” Reisa Sperling, MD, with the Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, told the panel.

The TRAILBLAZER-ALZ 2 trial used both amyloid and tau imaging to identify patients who were in the early stages of AD and were most likely to benefit from treatment.

However, it was the general consensus of the committee that if approved, tau PET imaging should not be a requirement for donanemab prescribing because it would create a barrier and “raise serious access concerns,” Montine said.

During the public comment period preceding the committee’s vote, 20 speakers shared strong opinions both for and against approval of donanemab, including comments from patients and caregivers who reported dramatic slowing of cognitive decline while taking donanemab.

“Historically, patients and doctors have believed there is nothing to slow Alzheimer’s progression. After a quarter of a century, we finally have evidence that we can bend the curve of cognitive decline with substantial reduction in amyloid,” Sperling commented.

In a statement sent to Medscape Medical News, Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said that it’s “encouraging to see that some patients essentially enter remission, where they achieve full amyloid clearance with donanemab, with no resurgence in substantial plaque buildup for nearly 4 years.”

“These findings are a direct result of biomarker tests that can detect, quantify, and monitor plaque buildup in the brain. Biomarkers will continue to revolutionize clinical trial design as we move towards developing drugs that target novel pathways guided by the biology of aging,” said Fillit.

Sperling noted that with current monoclonal antibodies, “we haven’t hit the full home run yet, but right now it is critical to do whatever we can have an impact to slow this terrible inexorably progressive neurodegenerative disease so that older people can enjoy this time with their families that they have worked all their lives to have.”

Fillit said that the committee’s endorsement “offers hope that donanemab will be approved in the coming months, but it’s important to look at this milestone in the larger treatment landscape for Alzheimer’s, which will entail a combination therapy and precision medicine approach.”

“If approved, donanemab will expand the first class of disease-modifying drugs, serving as the building blocks for future generations of drugs. Anti-amyloids are not a silver bullet, but they offer opportunities for patients to modify the course of the disease while the field works towards developing more novel therapies that target the underlying biology,” said Fillit.