Applicable Now, Research Radar

New Drug Shows Promise in Fight Against Cognitive Decline

On March 13, 2021, Eli Lilly & Co. announced encouraging news about an experimental drug designed to treat early Alzheimer’s disease (AD). The drug, donanemab, slowed the cognitive and functional decline of early-stage AD patients in a Phase 2 clinical trial and is now entering a Phase 3 trial, which – if successful – could lead to its regulatory approval.

The trial consisted of 257 patients and found that donanemab reduced cognitive and functional decline by 32% over a 76-week period. This improvement was measured by iADRS (integrated Alzheimer’s Disease Rating Scale) and was based on comparison to a control group. In addition, the patients who received the drug showed visible clearance of AD-specific amyloid plaques on brain PET scans and slowed the accumulation of tau – an AD biomarker  – in key brain regions, based on the scans’ analyses.

Classified as a monoclonal antibody, donanemab is an intravenous drug that targets a highly toxic form of beta amyloid known as pyroglutamate-3 beta amyloid. It dropped levels of the amyloid in cerebrospinal fluid both during and after treatment. It was largely well tolerated, with infusion-related reactions and sensitivities reported by 2.3% of the participants and symptomatic amyloid-related imaging abnormalities reported in 6% of the volunteers.

Eli Lilly & Co. warned in its press release that there is no guarantee that future study results will be consistent with the research to date. The company’s Phase 3 trial, called the TRAILBLAZER-ALZ 2 study, will include 500 patients with early stage AD and will run through early 2024. To learn more about the study, or to see if you prequalify to participate, visit www.trailblazer2study.com.

Primary Reference

Mintun M, Lo AC, et al. Donanemab slows progression of early symptomatic Alzheimer’s disease in phase 2 proof of concept trial. Presented virtually at the International Conference on Alzheimer’s & Parkinson Diseases™ 2021 (AD/PD™ 2021); March 9-14.

Additional References

  1. Eli Lilly & Co. press release. Mar 13, 2021. http://www.prnewswire.com/news-releases/lillys-donanemab-slowed-alzheimers-disease-progression-in-phase-2-trial-full-data-presented-at-adpd-2021-and-published-in-nejm-301246745.html.
  2. George J. Novel anti-amyloid slows cognitive decline in phase II Alzheimer trial. MedPage Today, Mar 13, 2021. https://www.medpagetoday.com/neurology/alzheimersdisease/91625?xid=nl_mpt_DHE_2021-03-15&eun=g1795093d0r.
  3. Mascarenhas L. Experimental Alzheimer’s drug could slow cognitive decline in patients, early results suggest. CNN online, Mar 13, 2021. https://www.cnn.com/2021/03/13/health/alzheimers-donanemab-cognitive-decline.
  4. Loftus P. Lilly Alzheimer’s drug shows modest benefit in clinical trial. The Wall Street Journal, March 13, 2021. https://www.wsj.com/articles/lilly-alzheimers-drug-shows-modest-benefit-in-clinical-trial-11615635001?mod=searchresults_pos4&page=1.