FDA Advisors Unanimously Recommend New Drug for Alzheimer’s Disease

The advisory committee to the U.S. Food and Drug Administration (FDA) unanimously voted on Monday to recommend the approval of donanemab to slow the progression of Alzheimer’s disease.
Data presented at the meeting showed that donanemab did not improve cognition in those who took it, and 7 percent experienced a slight neurocognitive decline after being on the drug for a year and a half.
However, brain imaging showed that 76.4 percent of patients achieved clearance of amyloid plaques.
Donanemab breaks down amyloid plaques in Alzheimer’s disease, an incurable neurodegenerative disease characterized by amyloid and tau protein deposits in the brain that are subsequently linked to neurocognitive decline. The drug is designed to slow the disease or improve cognitive decline in its early stages by breaking down amyloid and tau protein accumulation.
Dr. Nilufer Ertekin-Taner also voted in favor of recommending the drug but suggested more prolonged surveillance, especially for groups underrepresented in clinical trial data, such as African Americans, Latin Americans, and those with specific genetic variants that predispose them to a greater risk of Alzheimer’s.
Lilly’s clinical trial for donanemab initially tested whether the drug improved cognition and memory. However, the endpoint was changed during the study to evaluate instead whether the drug reduced amyloid plaque.
Due to this change, donanemab’s metric for efficacy was also changed.
At first, Lilly used a standardized test to evaluate cognition and memory. This was changed to an integrated Alzheimer Disease Rating Scale (iADRS) test, which measured amyloid reduction instead. This move was against FDA recommendations.
Finally, the agency noted an “imbalance in deaths” in the donanemab arm compared to placebo. The exact mortality numbers are uncertain because more than 20 percent of participants in both the donanemab and placebo groups discontinued the study.
Lilly said that the excess mortality is caused by the adverse events from the drug breaking up the amyloids in the brain. Still, the FDA reviewers said excess mortality could not be entirely explained by such adverse events or cerebral hemorrhage.
Dr. Curtis Schreiber, a neurologist, dementia specialist, and principal investigator at one of Lilly’s clinical trial sites, advocated donanemab’s approval.
The study found that monthly intravenous infusions of donanemab slowed Alzheimer’s progression over 76 weeks. However, the treatment group experienced more deaths compared to the placebo group, including three deaths directly linked to donanemab.
Additionally, 112 participants on donanemab discontinued the trial due to adverse events compared to 38 patients receiving a placebo.
Serious adverse events were reported in 17.4 percent of those given donanemab and 15.8 percent of those in the placebo group. Microhemorrhage events also more than doubled in the donanemab group.