Aducanumab

Aducanumab is a human monoclonal antibody that has been studied for the treatment of Alzheimer's disease (AD).[1] It was developed by Biogen Inc., which licensed the drug candidate from Neurimmune, its discoverer.[2] The antibody targets aggregated forms of β-amyloid found in the brains of people with Alzheimer's disease, in the hopes of reducing its buildup.[3] Biogen halted development of the drug in March 2019, after preliminary data from two phase III trials suggested it would not meet the primary endpoint.[4][5][6] As of January 2021, the decision by the FDA on the drug application is now delayed until June 7, 2021. [7]

Aducanumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
Targetbeta amyloid
Clinical data
Other namesBIIB037
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6472H10028N1740O2014S46
Molar mass145909 g·mol−1


Research

Interim results from the second Phase I study of the drug were reported in March 2015.[1][8]

A Phase Ib study was published in August 2016, based on one year of "monthly intravenous infusions" of aducanumab, with brain scans to measure amyloid plaques.[9]

Phase 3 clinical trials were ongoing in September 2016,[9] but were canceled in March 2019 after "an independent group's analysis show[ed] that the trials were unlikely to 'meet their primary endpoint.'"[10]

On 22 October 2019, Biogen announced that it would be restarting the FDA approval process for aducanumab stating that analysis of a larger dataset. [11][12][13] showed that the drug reduced clinical decline in patients with early Alzheimer's disease when given at higher doses.[14] In the first "EMERGE" trial, an analysis split by dose indicated that high doses reduced rate of decline by 23% versus placebo. A second identical trial "ENGAGE" failed to replicate this, with a non-significant 2% reduction in decline compared to placebo.[15][16][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 drug worked and suggested that the FDA not approve aducanumab, citing questionable efficacy and multiple “red flags” found with the data analysis.[18]. The FDA's final decision whether to green-light the drug was expected by March 2021.[19]

See also

References
  1. Fox C (April 28, 2015). "The Story of Biogen's Alzheimer's Drug, Aducanumab". Drug Discovery and Development. Archived from the original on 2015-07-01.
  2. Zacks R (November 20, 2007). "Biogen Inks $380 Million Deal with Swiss Company". Xconomy.
  3. Toyn J (May 2015). "What lessons can be learned from failed Alzheimer's disease trials?". Expert Review of Clinical Pharmacology. 8 (3): 267–9. doi:10.1586/17512433.2015.1034690. PMID 25860157. S2CID 35158630.
  4. Ducharme J (March 21, 2019). "Biogen Halts Promising Alzheimer's Drug Trials Due to Disappointing Results". Time. Retrieved 2019-03-21.
  5. Li Y (March 21, 2019). "Biogen posts its the worst day in 14 years after ending trial for blockbuster Alzheimer's drug". CNBC.
  6. Annett T. "Biogen Plunges More Than 25 Percent on Alzheimer's Setback". Bloomberg News.
  7. "FDA Delays Decision for Biogen's Alzheimer's Drug Until June". BioSpace.
  8. Herper M (March 20, 2015). "Biogen Drug Could Inspire New Hope For Alzheimer's Treatments". Forbes.
  9. Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. (September 2016). "The antibody aducanumab reduces Aβ plaques in Alzheimer's disease". Nature. 537 (7618): 50–6. Bibcode:2016Natur.537...50S. doi:10.1038/nature19323. PMID 27582220. S2CID 205250312.
  10. Li Y (21 March 2019). "Biogen shares plunge nearly 30% after ending trial for Alzheimer's drug Aducanumab". CNBC.
  11. Roberts M (22 October 2019). "First drug to slow Alzheimer's may be available soon". BBC News. Retrieved 22 October 2019.
  12. Foster L (October 26, 2019). "Drug 'could be biggest Alzheimer's development'". BBC News. Retrieved October 26, 2019.
  13. Kunkle F (December 6, 2019). "Biogen's potential new drug for Alzheimer's disease gets cautiously optimistic review following presentation". The Washington Post.
  14. Howard J, Gumbrecht J (October 23, 2019). "Drugmaker to seek approval for Alzheimer's treatment". CNN. Retrieved October 23, 2019.
  15. McNamara, Damien (May 28, 2020). "Mixed Results for Aducanumab in Two Phase 3 AD Trials". Medscape.
  16. Herper M (October 22, 2019). "In shocking reversal, Biogen to submit Alzheimer's drug for approval". STAT. Retrieved October 22, 2019. In one study, called Emerge, patients on the high-dose aducanumab had a 23% reduction in their rate of decline compared to those on placebo; those who were on the low dose were 11% lower than placebo, but that result was not statistically significant. But in the second trial, Engage, the decrease was only 2% in patients on the high dose.
  17. "Biogen Plans Regulatory Filing for Aducanumab in Alzheimer's Disease Based on New Analysis of Larger Dataset from Phase 3 Studies". Biogen. October 22, 2019. Retrieved October 22, 2019.
  18. Marchione, Marilynn; Perrone, Matthew (November 8, 2020). "FDA panel urges rejection of experimental Alzheimer's drug". Associated Press on MSNBC.
  19. "FDA panel rejects Biogen's new Alzheimer's drug". NBC News. 6 November 2020. Retrieved 16 December 2020.
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