Aducanumab was approved for medical use in the United States by the Food and Drug Administration (FDA) in June 2021,[12] in a controversial decision that led to the resignation of three advisers to the FDA in the absence of evidence that the medication is effective.[13][14][15] The FDA stated that it represents a first-of-its-kind treatment approved for Alzheimer's disease and that it is the first new treatment approved for Alzheimer's since 2003.[6] Aducanumab's approval is controversial for numerous reasons including ambiguous clinical trial results regarding efficacy, the high cost of the medication and the very high rate of serious adverse events.[16][15] The FDA considers it to be a first-in-class medication.[17]
In November 2020, a panel of outside experts for the FDA concluded that a pivotal study of aducanumab failed to show strong evidence that the medication worked, citing questionable efficacy and multiple red flags found with the data analysis.[18] There were also significant health risks associated with the medication; brain swelling or brain bleeding was found in 41% of patients enrolled in the studies.[19] Nevertheless, the medication was approved under the FDA's accelerated approval pathway, and the FDA requires Biogen to perform follow-up reviews to assure the medication is a safe and effective treatment for Alzheimer's disease.[6][20] The Office of Inspector General, US Department of Health and Human Services was asked to investigate interaction between the drug company and the FDA prior to the medication's approval.[21]
Biogen abandoned the drug in January 2024, for financial reasons.[22]
Lecanemab was jointly developed by Eisai and Biogen. It was granted accelerated approval for medical use in the United States in January 2023,[27] and fully approved by the FDA in July 2023.[24][28] Lecanemab was priced at $26,500 per year in the United States.[29] The European Medicines Agency ruled against approving the drug.[30] In Great Britain, the drug was approved but will not be covered by the English NHS due to its unfavorable benefit–cost ratio.
Donanemab was approved for medical use in the United States in July 2024 by the Food and Drug Administration.[32] Treatment is intended for patients with mild cognitive impairment or mild dementia stage of disease, which is the same population the treatment was studied in the clinical trials.[35]
Efficacy
A 2023 review found that "Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety."[36] 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."[37]
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 commentary, 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.[38] They also support running studies designed to distinguish between disease-modifying and symptomatic effects.[38]
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.[39]
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.[38]
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.[38]
Society and culture
Drug development
The approved anti-amyloid drugs were developed after years of unsuccessful attempts to develop a disease-modifying treatment for Alzheimer's disease.[40]
Cost
Concerns have been raised about the high cost of the drugs and accessibility to patients.[3]
^Lyu D, Lyu X, Huang L, Fang B (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. PMID37217078. S2CID258808777.
