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anti-Alzheimer monoclonal antibody

Indications: - investigational treatment of Alzheimer's disease - beta-amyloid antibodies - Aducanumab - Crezenumab - Donanemab - Gantenerumab - Lecanemab* - Solanezumab - microtubule-associated protein tau antibodies - Semorinemab * first beta-amyloid monoclonal antibody to receive traditional approval from the US Food & Drug Administration (FDA) [3] Contraindications: - anti-Alzheimer beta-amyloid monoclonal antibodies may fail to produce clinically meaningful benefits [6] - 2 groups of patients not likely to benefit* - amyloid-negative patients - amyloid-positive with a high plasma phospho-tau burden * plasma ptau217 useful for identifying patients unlikely to benefit [5] Adverse effects: - accelerated ventricular enlargement - may accelerate brain atrophy* * all anti-amyloid monoclonal antibodies accelerate brain shrinkage beyond atrophy associated with underlying Alzheimer's disease * pharmaceutical companies claim that atrophy is evidence of a reduction of amyloid & associated inflammation Laboratory: - plasma p-tau217 outperforms plasma p-tau181 & plasma p-tau231 & other plasma biomarkers of Alzheimer's disease in identifying which patients may benefit from an anti-beta-amyloid anti-Alzheimer monoclonal antibody [5] Mechanism of action: - pharmaeutical monocloncal antibodies all but semorinemab bind beta-amyloid - semorinemab binds to N-terminal part of microtubule-associated protein tau Notes: - CMS announces plan to cover anti-Alzheimer monoclonal antibodies [4]

Related

investigational therapies for treatment of Alzheimer's disease

Specific

aducanumab-avwa (Aduhelm) Crenezumab donanemab (Kisunla) gantenerumab lecanemab (Leqembi) semorinemab (binds MAP-tau) solanezumab

General

pharmaceutical agents for treatment of Alzheimer's disease (Alzheimer's agent) pharmaceutical monoclonal antibody

References

  1. Filippi M, Cecchetti G, Spinelli EG, Vezzulli P, Falini A, Agosta F. Amyloid-Related Imaging Abnormalities and beta-Amyloid-Targeting Antibodies: A Systematic Review JAMA Neurol. 2022 Mar 1;79(3):291-304. PMID: 35099507
  2. Alves F, Kallinowski P, Ayton S Accelerated Brain Volume Loss Caused by Anti-beta-Amyloid Drugs: A Systematic Review and Meta-analysis. Neurology. 2023. March 27. PMID: 36973044 https://n.neurology.org/content/early/2023/03/24/WNL.0000000000207156
  3. Rubin R Who Should - and Can - Get Lecanemab, the New Alzheimer Disease Drug? JAMA. Published online September 27, 2023. PMID: 37755935 https://jamanetwork.com/journals/jama/fullarticle/2810237
  4. CMS.gov June 22, 2023 CMS announces new details of plan to cover new Alzheimer's drugs. https://www.cms.gov/newsroom/fact-sheets/cms-announces-new-details-plan-cover-new-alzheimers-drugs
  5. George J Alzheimer's Blood Test Predicts Who Might Benefit Most From Anti-Amyloid Drugs. Novel two-cutoff approach may reduce need for confirmatory PET scans. MedPage Today December 5, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/107691 - Mattsson-Carlgren N, Collij LE, Stomrud E et al Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies. JAMA Neurol. Published online December 4, 2023. PMID: 38048096 https://jamanetwork.com/journals/jamaneurology/article-abstract/2812432
  6. Ebell MH, Barry HC, Baduni K, Grasso G. Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis. Ann Fam Med. 2024. 22(1):50-62 PMID: 38253509 Free article. Review. https://www.annfammed.org/content/22/1/50