Anti-amyloid drugs
Anti-amyloid drugs, also known as anti-amyloid antibodies (AAA),[1] are a class of monoclonal antibodies developed to treat Alzheimer's disease. The first drug in the class to be developed, in the early 2000s, was bapineuzumab, but it did not show effectiveness in later-stage trials.[2] The first drug to be FDA approved was aducanumab in 2021.[3]
Approved drugs[edit]
- Aducanumab (2021)[3]
- Lecanemab (2023)[4]
As of 2022 none of these drugs have been approved by the European Medicines Agency.[5]
Efficacy[edit]
A 2023 review found that "Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety."[6] A 2022 review finds "a statistically significant but slight clinical effect of these drugs emerges in patients with early AD after 18 months" and states, "The risk/benefit ratio of this class of drugs in early AD remains so far questionable after 18 months."[7]
From a 2023 statement by the European Association of Neurology and the European Psychiatric Association, "Anti-Aβ antibodies represent a significant advance in the treatment of AD, but their effectiveness is moderate and much work remains to be done to improve their efficacy, safety and accessibility."[2]
In a 2023 article in Brain Communications, the authors express concern that the results of the trials, which are based on scoring by patients and their caregivers, of these drugs could be confounded by unblinding produced by adverse effects. They also support running studies designed to distinguish between disease-modifying and symptomatic effects.[8]
Adverse effects[edit]
[edit]
Amyloid-related imaging abnormalities are a relatively uncommon but serious adverse effect.[7]
Accelerated brain volume loss[edit]
Brain volume loss is a symptom of Alzheimer's disease and is accelerated by anti-amyloid drugs developed to treat it. One meta-analysis found that people with mild cognitive impairment treated with anti-amyloid drugs would reach the brain volume associated with full Alzheimer's disease eight months earlier than those who received no such treatment. The significance of the brain volume loss caused by these drugs is unknown.[9]
The mechanism is not understood. Amyloid-related imaging abnormalities (ARIA) have been suggested as a possible cause of the accelerated brain volume loss. Others say it may be attributed to the reduction in amyloid plaques.[8]
Accelerated brain volume loss has been reported with lecanemab, aducanumab, donanemab, and other anti-amyloid drugs. Hippocampal, ventricular, and whole brain volumes are reported in studies and declines in all three have been found. However, the affected parts of the brain are not fully understood.[8]
Society and culture[edit]
Drug development[edit]
The approved anti-amyloid drugs were developed after years of unsuccessful attempts to develop a disease-modifying treatment for Alzheimer's disease.[10]
Cost[edit]
Concerns have been raised about the high cost of the drugs and accessibility to patients.[3]
References[edit]
- ^ Gandy, Sam (2023). "News & views: anti-amyloid antibodies and novel emerging approaches to Alzheimer's disease in 2023". Molecular Neurodegeneration. 18 (1). doi:10.1186/s13024-023-00656-x. PMC 10518943.
- ^ a b Perneczky, Robert; Dom, Geert; Chan, Andrew; Falkai, Peter; Bassetti, Claudio (11 September 2023). "Anti‐amyloid antibody treatments for Alzheimer's disease". European Journal of Neurology. doi:10.1111/ene.16049. hdl:10067/1987770151162165141. ISSN 1351-5101. PMID 37697714. S2CID 261694703.
- ^ a b c Brockmann, Rouen; Nixon, Joanna; Love, Bryan L.; Yunusa, Ismaeel (1 March 2023). "Impacts of FDA approval and Medicare restriction on antiamyloid therapies for Alzheimer's disease: patient outcomes, healthcare costs, and drug development". Lancet Regional Health - Americas. 20: 100467. doi:10.1016/j.lana.2023.100467. ISSN 2667-193X. PMC 9996432. PMID 36908502.
- ^ Hamilton, Jon (2023-07-06). "Alzheimer's drug Leqembi gets full FDA approval. Medicare coverage will likely follow". NPR. Retrieved 2023-11-26.
- ^ Villain, N.; Planche, V.; Levy, R. (December 2022). "High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 2: putative scenarios and timeline in case of approval, recommendations for use, implementation, and ethical considerations in France". Revue Neurologique. 178 (10): 999–1010. doi:10.1016/j.neurol.2022.08.002. PMID 36336488. S2CID 253349289.
- ^ Lyu, Diyang; Lyu, Xuanxin; Huang, Li; Fang, Boyan (July 2023). "Effects of three kinds of anti-amyloid-β drugs on clinical, biomarker, neuroimaging outcomes and safety indexes: A systematic review and meta-analysis of phase II/III clinical trials in Alzheimer's disease". Ageing Research Reviews. 88: 101959. doi:10.1016/j.arr.2023.101959. PMID 37217078. S2CID 258808777.
- ^ a b Villain, N.; Planche, V.; Levy, R. (1 December 2022). "High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects" (PDF). Revue Neurologique. 178 (10): 1011–1030. doi:10.1016/j.neurol.2022.06.012. ISSN 0035-3787. PMID 36184326.
- ^ a b c Liu, Kathy Y; Villain, Nicolas; Ayton, Scott; Ackley, Sarah F; Planche, Vincent; Howard, Robert; Thambisetty, Madhav (2 May 2023). "Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease". Brain Communications. 5 (3). doi:10.1093/braincomms/fcad175. PMID 37389302.
- ^ Alves, Francesca; Kalinowski, Pawel; Ayton, Scott (16 May 2023). "Accelerated Brain Volume Loss Caused by Anti–β-Amyloid Drugs: A Systematic Review and Meta-analysis". Neurology. 100 (20): e2114–e2124. doi:10.1212/WNL.0000000000207156. ISSN 0028-3878. PMC 10186239. PMID 36973044.
- ^ Perneczky, Robert; Dom, Geert; Chan, Andrew; Falkai, Peter; Bassetti, Claudio (11 September 2023). "Anti‐amyloid antibody treatments for Alzheimer's disease". European Journal of Neurology. doi:10.1111/ene.16049. hdl:10067/1987770151162165141. ISSN 1351-5101. PMID 37697714. S2CID 261694703.