A brand-new Alzheimers drug, donanemab, anticipated to be authorized by the FDA, reveals promising lead to slowing cognitive decline in patients with mild disease. Regardless of this, care is prompted due to potential serious negative effects, and issues have been raised over lack of variety in trials and the expected high expense of treatment.
The FDA is anticipated to authorize a 3rd Alzheimers drug, donanemab, signaling development in slowing the illness. The drug showed a 35% downturn in cognitive decline in clients with mild disease, however the benefit was less apparent in sophisticated cases.
Development in Alzheimers Treatment
With the impending approval of yet another Alzheimers drug by the Food and Drug Administration (FDA), the field is revealing indications of progress in the battle to slow the disease.
Nevertheless, these drugs are most reliable for those in the early stages of Alzheimers. According to Gil Rabinovici, MD, director of the University of California, San Francisco (UCSF) Alzheimers Disease Research Center, additional treatments will be needed for those with innovative disease.
He has actually suggested that this is “simply the opening chapter in a new era of molecular therapies for Alzheimers disease and related neurodegenerative disorders.”
Donanemab: A Promising New Alzheimers Drug
Rabinovici made these remarks in an editorial accompanying the results of the newest drug, donanemab, released on July 17, 2023, in JAMA. Like the two earlier Alzheimers drugs, aducanumab (Aduhelm) and lecanemab (Leqembi), donanemab is a monoclonal antibody. These drugs attack brain plaques made from a protein called amyloid, disrupting cell function and speeding up the spread of another protein, tau. Both amyloid and tau are included in Alzheimers disease progression.
The donanemab trial indicated that it slowed cognitive decrease by 35% compared to placebo in patients with low-to-intermediate levels of tau in the brain. Comparable results were reported with Leqembi, which got FDA approval earlier in the month. Clients in the donanemab trial had a 40% lower danger of progressing from mild cognitive disability to moderate dementia, or from moderate to moderate dementia.
Effectiveness and Risks of Donanemab
Donanemab was discovered to be more efficient at eliminating amyloid plaques compared to Aduhelm and Leqembi. It also decreased tau concentrations in the blood, but not in a crucial area of the brain.
In spite of these promising results, Rabinovici stressed the need for thorough analysis to comprehend how these findings impact client results.
Limitations of Donanemab
Clients with more advanced disease showed little to no benefit compared to those who got the placebo. In addition to the drugs possible serious adverse effects, this ought to motivate experts to “intend greater in developing more impactful and much safer treatments,” wrote Rabinovici, who is connected with the UCSF Memory and Aging Center, departments of Neurology, Radiology and Biomedical Imaging, as well as the Weill Institute for Neurosciences.
Donanemab needs to be limited to patients with low-to-intermediate levels of tau, suggesting mild illness. Further trials are underway to assess the efficacy of monoclonal antibodies in the earliest stage of the illness before symptoms appear.
Negative Effects and Precautions
Like the two other new Alzheimers drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that may include brain swelling and microbleeds. Threats were greater amongst clients with the APOE4 gene, which increases Alzheimers danger.
While ARIA has actually generally been handled securely in clinical trials, Rabinovici advises care as these drugs shift into real-world practice. He advocates for restricting access to patients with regular pre-treatment MRIs, conducting routine MRIs, and suspending or stopping treatment if ARIA occurs.
Ethical Concerns and Feasibility
A substantial constraint of the trial was the lack of ethnic and racial diversity. Just 8.6% of the 1,251 U.S. participants were non-white, raising ethical issues about the “generalizability of results to populations at greatest danger.” Rabinovici notes research studies that have revealed higher rates of dementia in Black and Latino populations.
Considering the forecasted high cost of donanemab and high patient demand, Rabinovici suggests restricting the treatment duration to the time needed to clear amyloid plaques from the brain. This method could “greatly enhance the feasibility of treatment for patients, clinicians, insurers, and health systems,” he specified.
Recommendations:
” Donanemab in Early Symptomatic Alzheimer DiseaseThe TRAILBLAZER-ALZ 2 Randomized Clinical Trial” by John R. Sims, MD; Jennifer A. Zimmer, MD; Cynthia D. Evans, PhD; Ming Lu, MD, MS, MPH; Paul Ardayfio, PhD; JonDavid Sparks, PhD; Alette M. Wessels, PhD; Sergey Shcherbinin, PhD; Hong Wang, PhD; Emel Serap Monkul Nery, MD; Emily C. Collins, PhD; Paul Solomon, PhD; Stephen Salloway, MD; Liana G. Apostolova, MD; Oskar Hansson, MD, PhD; Craig Ritchie, MD, PhD; Dawn A. Brooks, PhD; Mark Mintun, MD and Daniel M. Skovronsky, MD, PhD for the TRAILBLAZER-ALZ 2 Investigators, 17 July 2023, JAMA.DOI: 10.1001/ jama.2023.13239.
” Amyloid-Targeting Monoclonal Antibodies for Alzheimer Disease” by Gil D. Rabinovici, MD and Renaud La Joie, PhD, 17 July 2023, JAMA.DOI: 10.1001/ jama.2023.11703.
Co-Author: Renaud La Joie, PhD, of the UCSF Memory and Aging Center and Department of Neurology.
Funding: Rabinovici is supported by NIH P30-AG062422, R35-AG072362, R56-AG075744, u01-ag057195 and alzheimers Association ZEN-21-848216. La Joie is supported by NIH P30-AG062422, K99AG065501, and Alzheimers Association AARG-22-926899.
Disclosures: Rabinovici receives research study support and has supplied paid speaking with for Eli Lilly, the maker of donanemab. For other disclosures, please refer to the paper.
Rabinovici made these remarks in an editorial accompanying the results of the most current drug, donanemab, released on July 17, 2023, in JAMA. Like the two earlier Alzheimers drugs, aducanumab (Aduhelm) and lecanemab (Leqembi), donanemab is a monoclonal antibody. Both amyloid and tau are included in Alzheimers illness progression.
Like the 2 other new Alzheimers drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that might include brain swelling and microbleeds. Dangers were higher among clients with the APOE4 gene, which increases Alzheimers danger.