A Narrative Review on Preclinical/Clinical Trials on Aducanumab

  • Akriti Goel M M College of Pharmacy
  • Garima Chitkara University
  • Paras Jain Bhagwati College of Pharmacy
  • Seema Bansal M M College of Pharmacy
  • Hitesh Chopra Saveetha college of Engineering
  • Sumeet Gupta MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-133207, Ambala, Haryana, India
  • Satish Kumar Chaudhary Devi Lal University
  • Meenakshi Dhanawat Amity University
  • Navidha Aggarwal MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-133207, Ambala, Haryana, India
Keywords: Aducanumab, Alzheimer’s disease, Amyloid beta-peptides, Anti-dementia agents, Dementia, Antibodies, monoclonal

Abstract


The most widespread type of dementia, Alzheimer's disease (AD), is predicted to triple in global prevalence by 2050. AD has a substantial societal and economic impact across the world, negatively affecting both patients and their caregivers, as the disorder has few therapeutic alternatives. Aducanumab was the first monoclonal antibody approved in 2021 for the treatment of mild AD. Representing the first AD drug approval in 20 years and based on the concept of targeting amyloid-β (Aβ) as an immunisation treatment for AD, Aducanumab was demonstrated to reduce Aβ plaque formation in animal models and humans. This was used as a proxy of efficacy in AD clinical trials to slow disease progression and reduce cognitive decline in AD. Culminating from the Aβ hypothesis of AD that has dominated the focus of AD drug development since its inception, Aducanumab, for many, represents validation of the hypothesis and promise for the future. This review examines the antibody research, preclinical and clinical studies, that underpin the development of aducanumab as an AD medication. No single drug is generally likely to cure a complex, progressive and heterogeneous degenerative disorder, but it may act as a stepping stone towards greater understanding and potentially more effective treatment options. Time will ultimately tell in the case of aducanumab as to whether it is a small or large step in the correct or incorrect direction to unravel the mystery of this complex disorder and provide a worthwhile treatment.

References

Jeste DV, Mausbach B, Lee EE. Caring for caregivers/care partners of persons with dementia. Int Psychogeriatr. 2021 Apr;33(4):307–10. doi: 10.1017/S1041610221000557.

Bronzuoli MR, Iacomino A, Steardo L, Scuderi C. Targeting neuroinflammation in Alzheimer’s disease. J Inflamm Res. 2016 Nov 3:199–208. doi: 10.2147/JIR.S86958.

Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener. 2020;15:1–37. doi: 10.1186/s13024-020-00391-7.

Chen YG. Research progress in the pathogenesis of Alzheimer’s disease. Chin Med J (Engl). 2018 Jul 5;131(13):1618–24. doi: 10.4103/0366-6999.235112.

Plascencia-Villa G, Lin KH, Perry G, Jiang X, Kim Y. Multi-task graph neural network for Alzheimer’s disease drug repurposing using knowledge graph and multi-level evidence. doi: 10.21203/rs.3.rs-1261984/v1.

Briggs R, Kennelly SP, O’Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond). 2016 Jun;16(3):247–53. doi: 10.7861/clinmedicine.16-3-247.

Panza F, Seripa D, Solfriszi V, Imbimbo BP, Lozupone M, Leo A, et al. Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer’s disease patients. Expert Opin Emerg Drugs. 2016 Oct;21(4):377–91. doi: 10.1080/14728214.2016.1241232.

Dhillon S. Aducanumab: first approval. Drugs. 2021 Aug;81(12):1437–43. doi: 10.1007/s40265-021-01569-z.

Tian Hui Kwan A, Arfaie S, Therriault J, Rosa-Neto P, Gauthier S. Lessons learnt from the second generation of anti-amyloid monoclonal antibodies clinical trials. Dement Geriatr Cogn Disord. 2021 Feb 15;49(4):334–48. doi: 10.1159/000511506.

Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science. 1992 Apr 10;256(5054):184–5. doi: 10.1126/science.1566067.

Ricciarelli R, Fedele E. The amyloid cascade hypothesis in Alzheimer's disease: it's time to change our mind. Curr Neuropharmacol. 2017 Aug 1;15(6):926–35. doi: 10.2174/1570159X15666170116143743.

Barage SH, Sonawane KD. Amyloid cascade hypothesis: pathogenesis and therapeutic strategies in Alzheimer's disease. Neuropeptides. 2015 Aug;52:1–8. doi: 10.1016/j.npep.2015.06.008.

MacLeod R, Hillert EK, Cameron RT, Baillie GS. The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease. Future Sci OA. 2015 Nov 1;1(3):FSO11. doi: 10.4155/fso.15.9.

Wu HY, Kuo PC, Wang YT, Lin HT, Roe AD, Wang BY, et al. β-Amyloid induces pathology-related patterns of tau hyperphosphorylation at synaptic terminals. J Neuropathol Exp Neurol. 2018 Sep;77(9):814–26. doi: 10.1093/jnen/nly059.

Torcivia ML. Mimicking a common human T-cell leukemia mutation in Drosophila PLCgamma. Clark University; 2021.

Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535–62. doi: 10.1016/j.jalz.2018.02.018.

Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991 Jan;12:383–8. doi: 10.1016/0165-6147(91)90609-V.

Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L, et al. Evaluation of the safety and immunogenicity of synthetic Aβ42 (AN1792) in patients with AD. Neurology. 2005 Jan 11;64(1):94–101.

Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311–21. doi: 10.1056/NEJMoa1312889.

Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011 Sep;10(9):698–712. doi: 10.1038/nrd3505.

Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 1991 Sep;82(4):239–59. doi: 10.1007/BF00308809.

Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014 Aug;6:1–7. doi: 10.1186/alzrt269.

Abushouk AI, Elmaraezy A, Aglan A, Salama R, Fouda S, Fouda R, et al. Bapineuzumab for mild to moderate Alzheimer’s disease: a meta-analysis of randomised controlled trials. BMC Neurol. 2017 Dec;17:1–3. doi: 10.1186/s12883-017-0850-1.

Behl T, Kaur I, Sehgal A, Singh S, Sharma N, Makeen HA, et al. "Aducanumab" making a comeback in Alzheimer’s disease: an old wine in a new bottle. Biomed Pharmacother. 2022 Apr 1;148:112746. doi: 10.1016/j.biopha.2022.112746.

Beshir SA, Aadithsoorya AM, Parveen A, Goh SS, Hussain N, Menon VB. Aducanumab therapy to treat Alzheimer’s disease: a narrative review. Int J Alzheimers Dis. 2022;2022:9343514. doi: 10.1155/2022/9343514.

Budd Haeberlein S, Aisen PS, Barkhof F, Chalkias S, Chen T, Cohen S, et al. Two randomised phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimers Dis. 2022 Apr;9(2):197–210. doi: 10.14283/jpad.2022.30.

Mukhopadhyay S, Banerjee D. A primer on the evolution of aducanumab: the first antibody approved for treatment of Alzheimer’s disease. J Alzheimers Dis. 2021 Oct 12;83(4):1537–52. doi: 10.3233/JAD-215065.

Selkoe DJ. Alzheimer disease and aducanumab: adjusting our approach. Nat Rev Neurol. 2019 Jul;15(7):365–6. doi: 10.1038/s41582-019-0205-1.

Silvestro S, Valeri A, Mazzon E. Aducanumab and its effects on tau pathology: is this the turning point of amyloid hypothesis? Int J Mol Sci. 2022 Feb 11;23(4):2011. doi: 10.3390/ijms23042011.

Gao Y, Guo J, Zhang F, Li Y. Safety analysis of bapineuzumab in the treatment of mild to moderate Alzheimer's disease: a systematic review and meta-analysis. Comb Chem High Throughput Screen. 2024 Jan 1;27(1):40–7. doi: 10.2174/1386207326666230419095813.

Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med. 2011 Apr 6;3(77):77sr1. doi: 10.1126/scitranslmed.3002369.

Golde TE, Schneider LS, Koo EH. Anti-Aβ therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron. 2011 Jan 27;69(2):203–13. doi: 10.1016/j.neuron.2011.01.002.

Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016 Sep 1;537(7618):50–6. doi: 10.1038/nature19323.

Chiao P, Bedell BJ, Avants B, Zijdenbos AP, Grand'Maison M, O’Neill P, et al. Impact of reference and target region selection on amyloid PET SUV ratios in the phase 1b PRIME study of aducanumab. J Nucl Med. 2019 Jan;60(1):100–6. doi: 10.2967/jnumed.118.209130.

Arrighi HM, Barakos J, Barkhof F, Tampieri D, Jack C, Melançon D, et al. Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):106–12. doi: 10.1136/jnnp-2014-309493.

Brashear HR, Ketter N, Bogert J, Di J, Salloway SP, Sperling R. Clinical evaluation of amyloid-related imaging abnormalities in bapineuzumab phase III studies. J Alzheimers Dis. 2018;66(4):1409–24. doi: 10.3233/JAD-180675.

Klein G, Delmar P, Voyle N, Rehal S, Hofmann C, Abi-Saab D, et al. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis. Alzheimers Res Ther. 2019 Dec;11:1–2. doi: 10.1186/s13195-019-0559-z.

Iwatsubo T, Irisarry MC, Lewcock JW, Carrillo MC. Alzheimer's targeted treatments: focus on amyloid and inflammation. J Neurosci. 2023 Nov 22;43(47):7894–8. doi: 10.1523/JNEUROSCI.1576-23.2023.

Boche D, Denham N, Holmes C, Nicoll JA. Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis. Acta Neuropathol. 2010 Sep;120:369–84. doi: 10.1007/s00401-010-0719-5.

Kastanenka KV, Bussiere T, Shakerdge N, Qian F, Weinreb PH, Rhodes K, et al. Immunotherapy with aducanumab restores calcium homeostasis in Tg2576 mice. J Neurosci. 2016 Dec 14;36(50):12549–58. doi: 10.1523/JNEUROSCI.2080-16.2016.

Bastrup J, Hansen KH, Poulsen TB, Kastaniegaard K, Asuni AA, Christensen S, et al. Anti-Aβ antibody aducanumab regulates the proteome of senile plaques and closely surrounding tissue in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2021 Jan;79(1):249–65. doi: 10.3233/JAD-200715.

Snapinn S, Chen MG, Jiang Q, Koutsoukos T. Assessment of futility in clinical trials. Pharm Stat. 2006 Oct;5(4):273–81. doi: 10.1002/pst.216.

Arndt JW, Qian F, Smith BA, Quan C, Kilambi KP, Bush MW, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Sci Rep. 2018 Apr 23;8(1):6412. doi: 10.1038/s41598-018-24501-0.

Abyadeh M, Gupta V, Gupta V, Chitranshi N, Wu Y, Amirkhani A, et al. Comparative analysis of aducanumab, zagotenemab and pioglitazone as targeted treatment strategies for Alzheimer’s disease. Aging Dis. 2021 Dec 1;12(8):1964. doi: 10.14336/AD.2021.0719.

Sabbagh MN, Cummings J. Open peer commentary to “Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen December 2019”. Alzheimers Dement. 2020 Nov;17(4):702. doi: 10.1002/alz.12235.

Haeberlein SB, von Hehn C, Tian Y, Chalkias S, Muralidharan KK, Chen T, et al. EMERGE and ENGAGE topline results: Phase 3 studies of aducanumab in early Alzheimer’s disease. Alzheimers Dement. 2020 Jul 29;16(S9):e047259. doi: 10.1002/alz.047259.

Chang Y, Song T, Monaco J, Ivanova A. Futility stopping in clinical trials, optimality and practical considerations. J Biopharm Stat. 2020 Nov;30(6):1050–9. doi: 10.1080/10543406.2020.1818253.

Viglietta V, O'Gorman J, Williams L, Tian Y, Sandrock A, Doody R, et al. Randomised, double-blind, placebo-controlled studies to evaluate treatment with aducanumab (BIIB037) in patients with early Alzheimer’s disease: Phase 3 study design (S1.003). Neurology. 2016 Apr 5;86(16_Supplement):S1-003. doi: 10.1212/WNL.86.16_supplement.S1.003.

Howard R, Liu KY. Questions EMERGE as Biogen claims aducanumab turnaround. Nat Rev Neurol. 2020 Feb;16(2):63–4. doi: 10.1038/s41582-019-0295-9.

VandeVrede L, Gibbs DM, Koestler M, La Joie R, Ljubenkov PA, Provost K, et al. Symptomatic amyloid-related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab. Alzheimers Dement (DADM). 2020;12(1):e12101. doi: 10.1002/dad2.12101.

Tolar M, Abushakra S, Hey JA, Porsteinsson A, Sabbagh M. Aducanumab, gantenerumab, BAN2401 and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther. 2020 Aug 12;12(1):95. doi: 10.1186/s13195-020-00663-w.

Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M. Aducanumab: appropriate use recommendations. J Prev Alzheimers Dis. 2021 Apr 1;8(4):398–410. doi: 10.14283/jpad.2021.41.

Leinenga G, Koh WK, Götz J. A comparative study of the effects of aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease. Alzheimers Res Ther. 2021 Dec;13:1–4. doi: 10.1186/s13195-021-00809-4.

Anderson TS, Ayanian JZ, Souza J, Landon BE. Representativeness of participants eligible to be enrolled in clinical trials of aducanumab for Alzheimer disease compared with Medicare beneficiaries with Alzheimer disease and mild cognitive impairment. JAMA. 2021 Oct 26;326(16):1627–9. doi: 10.1001/jama.2021.15286.

Hershey LA, Tarawneh R. Clinical efficacy, drug safety and surrogate endpoints: has aducanumab met all of its expectations?. Neurology. 2021 Sep 14;97(11):517–8. doi: 10.1212/WNL.0000000000012453.

Nistico R, Borg JJ. Aducanumab for Alzheimer’s disease: a regulatory perspective. Pharmacol Res. 2021 Sep;171:105754. doi: 10.1016/j.phrs.2021.105754.

Ashique S, Sirohi E, Kumar S, Rihan M, Mishra N, Bhatt S, et al. Aducanumab in Alzheimer’s disease: a critical update. Curr Med Chem. 2024 Sep 1;31(31):5004–26. doi: 10.2174/0929867331666230727103553.

Salloway S, Chalkias S, Barkhof F, Burkett P, Barakos J, Purcell D, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022 Jan;79(1):13–21. doi: 10.1001/jamaneurol.2021.4161.

Vellas BJ. The geriatrician, the primary care physician, aducanumab and the FDA decision: from frustration to new hope. J Nutr Health Aging. 2021 Jul;25:821–3. doi: 10.1007/s12603-021-1657-8.

Weiner MW, Aisen PS, Beckett LA, Green RC, Jagust W, Morris JC, et al. How will aducanumab approval impact AD research?. J Prev Alzheimers Dis. 2021 Oct;8:391–2. doi: 10.14283/jpad.2021.46.

Huang LK, Kuan YC, Lin HW, Hu CJ. Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update. J Biomed Sci. 2023 Oct 2;30(1):83. doi: 10.1186/s12929-023-00976-6.

Heidebrink JL, Paulson HL. Lessons learned from approval of aducanumab for Alzheimer's disease. Annu Rev Med. 2024 Jan 29;75(1):99–111. doi: 10.1146/annurev-med-051022-043645.

Rahman A, Hossen MA, Chowdhury MF, Bari S, Tamanna N, Sultana SS, et al. Aducanumab for the treatment of Alzheimer's disease: a systematic review. Psychogeriatrics. 2023 May;23(3):512–22. doi: 10.1111/psyg.12944.

Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021 May 6;384(18):1691–704. doi: 10.1056/NEJMoa2100708.

Rezai AR, D’Haese PF, Finomore V, Carpenter J, Ranjan M, Wilhelmsen K, et al. Ultrasound blood–brain barrier opening and aducanumab in Alzheimer’s disease. N Engl J Med. 2024 Jan 4;390(1):55–62. doi: 10.1056/NEJMoa2308719.

Wojtunik-Kulesza K, Rudkowska M, Orzeł-Sajdłowska A. Aducanumab—hope or disappointment for Alzheimer’s disease. Int J Mol Sci. 2023 Feb 22;24(5):4367. doi: 10.3390/ijms24054367.

Tampi RR, Forester BP, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs Context. 2021 Oct 4;10:1–12. doi: 10.7573/dic.2021-7-3.

Grover S, Jain S. Aducanumab: a review of the first approved amyloid-targeting antibody for Alzheimer’s disease. Drugs Ther Perspect. 2022 Oct;38(10):443–54. doi: 10.1007/s40267-022-00944-4.

Alexander GC, Emerson S, Kesselheim AS. Evaluation of aducanumab for Alzheimer disease: scientific evidence and regulatory review involving efficacy, safety and futility. JAMA. 2021 May 4;325(17):1717–8. doi: 10.1001/jama.2021.3854.

Lipsman N, Meng Y, Bethune AJ, Huang Y, Lam B, Masellis M, et al. Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat Commun. 2018 Jul 25;9(1):2336. doi: 10.1038/s41467-018-04529-6.

Zhang J, Zhang Y, Wang J, Xia Y, Zhang J, Chen L. Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies. Signal Transduct Target Ther. 2024 Aug 23;9(1):211. doi: 10.1038/s41392-024-01911-3.

Hansen SB, Wang H. The shared role of cholesterol in neuronal and peripheral inflammation. Pharmacol Ther. 2023 Jun 29;308:108486. doi: 10.1016/j.pharmthera.2023.108486.

Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):e2102191118. doi: 10.1073/pnas.2102191118.

Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer's disease drug development pipeline: 2023. Alzheimers Dement (N Y). 2023 Apr;9(2):e12385. doi: 10.1002/trc2.12465.

Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord. 2013 Jan;6(1):19–33. doi: 10.1177/1756286420930020.

Teipel SJ, Temp AG, Lutz MW. Bayesian meta-analysis of phase 3 results of aducanumab, lecanemab, donanemab and high-dose gantenerumab in prodromal and mild Alzheimer's disease. Alzheimers Dement (N Y). 2024 Jan;10(1):e12454. doi: 10.1002/trc2.12454.

Liu MJ, Long Z, Li F, Shi X, Shen YF, Liu ML. Distinct effects of aducanumab and lecanemab on intraneuronal endogenous Aβ42 and phosphorylated tau in Alzheimer’s disease treatment. bioRxiv. 2024 Feb 6:2024.02.06.579113. doi: 10.1101/2024.02.06.579113.

Castrillo-Viguera C, Chalkias S, Burkett P, Wu S, Chen H, Harrison K, et al. EMBARK: a Phase 3b, open-label, single-arm, safety study to evaluate the long-term safety and efficacy of aducanumab in eligible participants with Alzheimer’s disease (2448). Neurology. 2021 Apr 13;96(15 Suppl):2448. doi: 10.1212/WNL.96.15_supplement.2448.

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease and implications for ongoing trials of aducanumab. N Engl J Med. 2023 Jan;388(1):9–21. doi: 10.1056/NEJMoa2212948.

A study to evaluate the efficacy and safety of aducanumab in participants with early Alzheimer's disease (ENVISION). ClinicalTrials.gov [Internet]. 2022 [Cited: 23 Dec 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05310071.

Murphy J, Aisen P, Barkhof F, Castrillo-Viguera C, Cheng W, Cohen S, et al. ENVISION: a phase 3b/4 randomised, double-blind, placebo-controlled, parallel-group study to verify the clinical benefit of aducanumab in participants with early Alzheimer’s disease. Alzheimers Dement. 2022 Dec;18:e069428. doi: 10.1002/alz.069428.

Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: an analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement. 2021 Apr;17(4):696–701. doi: 10.1002/alz.12213.

Aducanumab (ADUHELM) for the treatment of Alzheimer's disease: a Phase 3 study to clear amyloid plaques. ClinicalTrials.gov [Internet]. 2021 [Cited: 23 Dec 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT03639987.

FDA grants accelerated approval for Alzheimer's drug. FDA News Release. [Internet]. Jun 2021 [Cited: 23 Dec 2024]. Available from: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug.

A study to evaluate the safety and efficacy of aducanumab in early Alzheimer's disease (EMERGE). ClinicalTrials.gov [Internet]. 2018 [Cited: 23 Dec 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT02477800.

Sevigny J, Chiao P, Williams L, Chen T, Ling Y, O'Gorman J, et al. O4‑04‑05: Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with prodromal or mild Alzheimer's disease: interim results of a randomised, double-blind, placebo-controlled, phase 1b study. Alzheimers Dement. 2015 Jul;11(7S Pt 6):P277. doi: 10.1016/j.jalz.2015.07.367.

A study to evaluate the safety and efficacy of aducanumab in early Alzheimer's disease (ENGAGE). ClinicalTrials.gov [Internet]. 2018 [Cited: 23 Dec 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT02477839.

Published
2026/04/29
Section
Review article