donanemab (Kisunla)
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Indications
- anti-Alzheimer monoclonal antibody (FDA-approved)
- treatment of early symptomatic Alzheimer's disease with confirmed amyloid pathology
- includes Alzheimer's patients with mild cognitive impairment & mild dementia[8]
Dosage
- 700 mg intravenously every 4 weeks for 3 doses
- followed with 1400 mg intravenously every 4 weeks[11]
Monitor
- surveillance MRI should be performed before the 2nd, 3rd, & 4th infusions[11]
- MRI if symptoms suspicious for ARIA
- consider stopping therapy if follow-up amyloid PET is read as negative (12-18 months after initiation)[11]
- joint ALZNET registry
Adverse effects
- amyloid-related imaging abnormalities (ARIA), ARIA with edema (ARIA-E) ARIA with hemosiderin deposition (ARIA-H)*[11]
* patients homozygous for apoE4 allele with higher incidence of ARIA, including symptomatic, serious, & severe radiographic ARIA, compared to heterozygotes & noncarriers[11]
- drug adverse effects of anti-Alzheimer monoclonal antibody
- drug adverse effects of pharmaceutical monoclonal antibodies
Drug interactions
- antiplatelet drugs increase risk intracerebral hemorrhage
- anticoagulants increase risk of intracerebral hemorrhage
- thrombolytic agents increase risk of intracerebral hemorrhage
Mechanism of action
- immunoglobulin G1 monoclonal antibody directed against insoluble, modified, N-terminal truncated form of beta-amyloid present only in established amyloid plaques
Clinical trials
- small phase 2 trial[1]
- granted breakthrough therapy designation
- Eli Lilly will seek accelerated approval
- claims showed signs of slowing cognitive decline & improving activities of daily living in early Alzheimer's disease[1][2]
- donanemab slows clinical progression in symptomatic Alzheimer's disease with beta-amyloid & tau pathology at 76 weeks[6]
Notes
- FDA has denied accelerated approval Jan 2023
- Lily announces donanemab significantly slowed cognitive and functional decline in phase 3 study of early Alzheimer's disease[5]
- 3 of 11 advisers who recommended approval of donanemab received direct payments or research funding from its manufacturer, Lilly[9]
- 2 advisors had ties to Roche, developmental partner to Lilly
- 2 other advisors have patents of anti-amyloid antibodies[9]
- NICE rejects donanemab due to cost & significant health risks[10]
More general terms
Additional terms
References
- ↑ 1.0 1.1 1.2 George J Novel Alzheimer's Drug Appears to Slow Decline - Donanemab shows positive results in small phase II study, says drugmaker. MedPage Today January 11, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/90636
George J Novel Anti-Amyloid Slows Cognitive Decline in Phase II Alzheimer Trial. Though benefit was limited in 76-week study, specialists see reasons for optimism. MedPage Today March 13, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/91625
Brause D Novel Alzheimer's Drug Slows Cognitive Decline in Phase 2 Trial Medscape - Mar 13, 2021. https://www.medscape.com/viewarticle/947410
Mintun MA, Lo AC, Duggan Evans D Donanemab in Early Alzheimer's Disease. N Engl J Med 2021; 384:1691-1704. May 6, Online: March 13, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33720637 https://www.nejm.org/doi/full/10.1056/NEJMoa2100708 - ↑ 2.0 2.1 Hung WH Alzheimer's Disease Treatment on the Horizon or False Dawn? Medscape - Jul 14, 2021. https://www.medscape.com/viewarticle/954015
- ↑ Shcherbinin A, Evans CD, Lu M et al Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes. The TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA Neurol. Published online September 12, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36094645 https://jamanetwork.com/journals/jamaneurology/fullarticle/2795844
- ↑ Bender E FDA Says No to Accelerated Approval for Alzheimer's Drug Medscape. Jan 20, 2023 https://www.medscape.com/viewarticle/987276
- ↑ 5.0 5.1 Lily Investors. News Release. May 3, 2023 Lilly's Donanemab Significantly Slowed Cognitive and Functional Decline in Phase 3 Study of Early Alzheimer's Disease. https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional
- ↑ 6.0 6.1 Sims JR, Zimmer JA, Evans CD et al Donanemab in Early Symptomatic Alzheimer Disease. The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. Published online July 17, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37459141 PMCID: PMC10352931 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2807533
- ↑ 7.0 7.1 AMA Morning Rounds. June 11, 2024
George J Unanimous Thumbs-Up From FDA Advisors for Alzheimer's Drug. Advisory committee decision smooths the way for eventual FDA approval. MedPage Today June 10, 2024 https://www.medpagetoday.com/neurology/alzheimersdisease/1105758 - ↑ 8.0 8.1 George J FDA OKs Another Drug for Early Alzheimer's Disease. Decision gives patients a second anti-amyloid treatment option. MedPage Today July 2, 2024 https://www.medpagetoday.com/neurology/alzheimersdisease/110934
- ↑ 9.0 9.1 9.2 Lenzer J, Brownlee S. Donanemab: Conflicts of interest found in FDA committee that approved new Alzheimer's drug. BMJ 2024;386:q2010 PMID: https://www.ncbi.nlm.nih.gov/pubmed/39322239 https://www.bmj.com/content/386/bmj.q2010
- ↑ 10.0 10.1 Mahase E NICE rejects Alzheimer's drug donanemab owing to cost and "significant health risks" BMJ 2024;387:q2342 PMID: https://www.ncbi.nlm.nih.gov/pubmed/39442962 https://www.bmj.com/content/387/bmj.q2342
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 Brooks M Expert Guidance Issued for Real-World Use of Donanemab Medscape. Oct 30, 2024 https://www.medscape.com/viewarticle/expert-guidance-issued-real-world-use-donanemab-2024a1000jwa
- ↑ Kinsula (donanemab-azbt) injection for IV infusion 350 mg/20 mL https://kisunla.lilly.com/hcp/support-resources