The FDA advisory committee recently voted 11-0 in support of the investigational drug donanemab for treating early Alzheimer’s disease. The committee concluded that the benefits of donanemab outweighed its risks for patients with mild cognitive impairment and mild dementia. Furthermore, they agreed unanimously that the available data demonstrated the drug’s effectiveness in treating Alzheimer’s disease in this specific population.
While the overall consensus was in favor of donanemab, concerns were raised during the meeting about the lack of representation of African-American and Hispanic populations in the clinical trials. Committee members highlighted the importance of obtaining data from diverse populations to ensure that the positive findings of the drug can be generalized to all individuals with Alzheimer’s disease.
One of the main risks associated with donanemab is amyloid-related imaging abnormalities (ARIA), including ARIA with edema or effusion (ARIA-E) and ARIA with microhemorrhages and hemosiderin deposits (ARIA-H). Despite these risks, FDA advisors suggested that safeguards could be put in place to manage ARIA effects. The importance of monitoring and addressing these risks through MRI programs and training was emphasized during the discussion.
Neurologist Marwan Sabbagh, who was not directly involved in the donanemab trials, reflected on the perspectives of Alzheimer’s patients during the public hearing. He highlighted the significant decline and loss of autonomy that patients with Alzheimer’s face, juxtaposed against the relatively low risk of symptomatic ARIA associated with the drug. This perspective underscores the urgent need for effective treatments for Alzheimer’s disease.
Donanemab was evaluated in the phase III TRAILBLAZER-ALZ 2 trial, which included 1,736 early Alzheimer’s patients. The trial results showed that the drug met its primary endpoint by slowing decline in the Integrated Alzheimer’s Disease Rating Scale (iADRS) compared to placebo. Additionally, donanemab demonstrated less decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 76 weeks, further supporting its potential effectiveness in treating Alzheimer’s disease.
If approved, donanemab will be the third amyloid-targeted drug to enter the market, following the controversial aducanumab (Aduhelm) and lecanemab (Leqembi). Aducanumab received accelerated approval but was later abandoned, while lecanemab received full FDA approval. Donanemab’s approval would provide another option for the treatment of Alzheimer’s disease, potentially offering new hope for patients and caregivers.
The unanimous support for donanemab by the FDA advisory committee represents a significant step forward in the treatment of early Alzheimer’s disease. Despite concerns about data representation and risks associated with the drug, the committee’s decision reflects the urgent need for effective therapies for Alzheimer’s patients. Moving forward, continued research and monitoring will be essential to ensure the safety and efficacy of donanemab in diverse populations.
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