Donanemab slows progression of Alzheimer’s disease

Key takeaways:

• The low to medium tau population experienced a 35.1% slowing of disease progression.
• The treatment group experienced a 38.6% lower risk of progression to the next disease stage compared with placebo.

Donanemab “significantly” slowed clinical progression of Alzheimer’s disease in those with low to medium or high tau pathology, according to a poster presentation at the Alzheimer’s Association International Conference.

“Today’s results are promising, with donanemab slowing cognitive decline by 35% in patients with early-stage Alzheimer’s disease, making it all the more apparent that antiamyloid therapies will serve as the first line of defense in the arsenal of drugs needed to treat this disease,” Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said in a press release.

In a 76-week phase 3 study of 1,320 randomized participants with a mean age of 73 years, Mark Mintun, MD, and colleagues studied 24 gated outcomes. Participants either received donanemab at 700 mg for the first three doses and 1,400 mg thereafter, or an intravenously administered placebo for up to 72 weeks. Amyloid plaque level was assessed at 24 weeks and 52 weeks, and if it was less than 11 Centiloids on a PET scan or less than 25 but greater or equal to 11 Centaloids on two consecutive PET scans, donanemab was switched to placebo.

The researchers found that of the 24 gated outcomes, 23 were statistically significant.

When examining the difference in integrated AD Rating Scale scores at 76 weeks between the donanemab and placebo groups, researchers reported that the low to medium tau population on donanemab experienced a 35.1% slowing of disease progression. Mintun and colleagues also reported that participants in the treatment group experienced a 38.6% lower risk of progression to the next disease stage compared with the placebo group.

The donanemab group experienced a 17.4% incidence of serious adverse events, compared with 15.8% in the placebo group, with three deaths related to donanemab treatment, resulting from amyloid-related imaging abnormality and infusion-related reactions.

“In the next wave of trial design, researchers must begin conducting combination therapy clinical trials that use precision biomarkers to gain a deeper understanding of how multiple drugs interact with one another as part of a broader treatment strategy for Alzheimer’s,” Fillit said.

References:

• Sims JR, et al. JAMA. 2023;doi:10.1001/jama.2023.13239.
• ADDF statement on new results from Donanemab’s TRAILBLAZERALZ. https://www.alzdiscovery.org/news-room/announcements/addf-statement-on-new-results-from-donanemabs-trailblazer-alz-2-trial. Published July 17, 2023. Accessed July 18, 2023.