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donanemab (Kisunla)

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 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 - Advisory Commmitte recommends FDA-approved June 2024 [7] - 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]

Interactions

drug adverse effects of anti-Alzheimer monoclonal antibody

Related

investigational therapies for treatment of Alzheimer's disease

General

anti-Alzheimer monoclonal antibody

References

  1. 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: 33720637 https://www.nejm.org/doi/full/10.1056/NEJMoa2100708
  2. Hung WH Alzheimer's Disease Treatment on the Horizon or False Dawn? Medscape - Jul 14, 2021. https://www.medscape.com/viewarticle/954015
  3. 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: 36094645 https://jamanetwork.com/journals/jamaneurology/fullarticle/2795844
  4. Bender E FDA Says No to Accelerated Approval for Alzheimer's Drug Medscape. Jan 20, 2023 https://www.medscape.com/viewarticle/987276
  5. 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. 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: 37459141 PMCID: PMC10352931 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2807533
  7. 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. 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. Lenzer J, Brownlee S. Donanemab: Conflicts of interest found in FDA committee that approved new Alzheimer's drug. BMJ 2024;386:q2010 PMID: 39322239 https://www.bmj.com/content/386/bmj.q2010
  10. Mahase E NICE rejects Alzheimer's drug donanemab owing to cost and "significant health risks" BMJ 2024;387:q2342 PMID: 39442962 https://www.bmj.com/content/387/bmj.q2342
  11. 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
  12. Kinsula (donanemab-azbt) injection for IV infusion 350 mg/20 mL https://kisunla.lilly.com/hcp/support-resources