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Aducanumab

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Aducanumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
Targetbeta amyloid
Clinical data
Trade namesAduhelm
Other namesBIIB037
License data
Routes of
administration		Intravenous
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Elimination half-life24.8 days[3]
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6472H10028N1740O2014S46
Molar mass145912.34 g·mol−1

Aducanumab, sold under the brand name Aduhelm, is used to treat Alzheimer's disease (AD). It is an amyloid beta-directed antibody.

Aducanumab targets aggregated forms of β-amyloid found in the brains of people with Alzheimer's disease, in the hopes of reducing its buildup.[4]

Aducanumab was approved for medical use in the United States in June 2021, and it represents a first-of-its-kind treatment approved for Alzheimer's disease.[2] It is the first new treatment approved for Alzheimer's since 2003, and is the first therapy that targets the fundamental pathophysiology of the disease.[2]

Medical uses

Aducanumab is indicated for the treatment of Alzheimer's disease.[2]

History

Aducanumab was developed by Biogen Inc., which licensed the drug candidate from Neurimmune, its discoverer.[5] 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.[6][7][8]

Researchers evaluated the efficacy of aducanumab in three separate studies representing a total of 3,482 participants.[2] The studies consisted of double-blind, randomized, placebo-controlled dose-ranging studies in participants with Alzheimer's disease.[2] Participants receiving the treatment had significant dose-and time-dependent reduction of amyloid beta plaque, while participants in the control arm of the studies had no reduction of amyloid beta plaque.[2]

Society and culture

Economics

Treatment is estimated to cost US$56,000 per year, and Biogen's CEO stated that they would maintain this price for at least four years.[9]

Controversy

In November 2020, a panel of outside experts for the U.S. Food and Drug Administration (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.[10] The final decision of the FDA to green-light the drug was made on June 7, 2021.[11] The drug was considered controversial as clinical trials gave conflicting results on its effectiveness.[12][13]

Research

Aducanumab is a human IgG1 monoclonal antibody that primarily binds to Aβ aggregates, soluble oligomers and also insoluble fibrils and has been studied for the treatment of Alzheimer's disease (AD).[14][15] However, it does not seem to target Aβ monomers. Aducanumab analogue can cross the blood-brain barrier and engage its target efficiently, thus clearing beta amyloid toxicity. The effects can be monitored by positron emission tomography (PET)[15].

Interim results from the second Phase I study of the drug were reported in March 2015.[14][16]

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.[17] Phase 2 trials were not required by the FDA and not conducted by Biogen for aducanumab, a decision that received criticism from some experts[18][19]. Phase 3 trials followed the conclusion of Phase 1 studies. Phase 3 clinical trials were ongoing in September 2016,[17] but were canceled in March 2019 after "an independent group's analysis show[ed] that the trials were unlikely to 'meet their primary endpoint.'"[20]

On 22 October 2019, Biogen announced that it would be restarting the FDA approval process for aducanumab stating that analysis of a larger dataset [21][22][23] showed that the drug reduced clinical decline in patients with early Alzheimer's disease when given at higher doses.[24] 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.[25][26][27]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ a b c d e f g "FDA Grants Accelerated Approval for Alzheimer's Drug". U.S. Food and Drug Administration (FDA) (Press release). 7 June 2021. Retrieved 7 June 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ a b "Aduhelm (aducanumab-avwa) injection, for intravenous use" (PDF). Biogen. Retrieved 8 June 2021.
  4. ^ 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.
  5. ^ Zacks R (20 November 2007). "Biogen Inks $380 Million Deal with Swiss Company". Xconomy.
  6. ^ Ducharme J (21 March 2019). "Biogen Halts Promising Alzheimer's Drug Trials Due to Disappointing Results". Time. Retrieved 21 March 2019.
  7. ^ Li Y (21 March 2019). "Biogen posts its the worst day in 14 years after ending trial for blockbuster Alzheimer's drug". CNBC.
  8. ^ Annett T. "Biogen Plunges More Than 25 Percent on Alzheimer's Setback". Bloomberg News.
  9. ^ "Biogen CEO: committed to gathering new data on FDA-approved Alzheimer's drug".
  10. ^ Marchione, Marilynn; Perrone, Matthew (6 November 2020). "FDA panel urges rejection of experimental Alzheimer's drug". Associated Press.
  11. ^ "FDA's Decision to Approve New Treatment for Alzheimer's Disease". U.S. Food and Drug Administration (FDA). 7 June 2021. Retrieved 7 June 2021.
  12. ^ "US approves first new Alzheimer's drug in 20 years". BBC News Online. 7 June 2021.
  13. ^ "F.D.A. Approves Alzheimer's Drug Despite Fierce Debate Over Whether It Works". The New York Times. 7 June 2021.
  14. ^ a b Fox C (28 April 2015). "The Story of Biogen's Alzheimer's Drug, Aducanumab". Drug Discovery and Development. Archived from the original on 1 July 2015.
  15. ^ a b Ghosh, Shampa; Durgvanshi, Shantanu; Agarwal, Shreya; Raghunath, Manchala; Sinha, Jitendra Kumar (6 October 2020). "Current Status of Drug Targets and Emerging Therapeutic Strategies in the Management of Alzheimer's Disease". Current Neuropharmacology. 18 (9): 883–903. doi:10.2174/1570159X18666200429011823.
  16. ^ Herper M (20 March 2015). "Biogen Drug Could Inspire New Hope For Alzheimer's Treatments". Forbes.
  17. ^ a b 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.
  18. ^ Karlawish, Jason (30 May 2021). "If the FDA approves Biogen's Alzheimer's treatment, I won't prescribe it". STAT. Retrieved 7 June 2021.
  19. ^ Belluck, Pam; Robbins, Rebecca (5 June 2021). "Alzheimer's Drug Poses a Dilemma for the F.D.A." The New York Times. Retrieved 7 June 2021.
  20. ^ Li Y (21 March 2019). "Biogen shares plunge nearly 30% after ending trial for Alzheimer's drug Aducanumab". CNBC.
  21. ^ Roberts M (22 October 2019). "First drug to slow Alzheimer's may be available soon". BBC News. Retrieved 22 October 2019.
  22. ^ Foster L (26 October 2019). "Drug 'could be biggest Alzheimer's development'". BBC News. Retrieved 26 October 2019.
  23. ^ Kunkle F (6 December 2019). "Biogen's potential new drug for Alzheimer's disease gets cautiously optimistic review following presentation". The Washington Post.
  24. ^ Howard J, Gumbrecht J (23 October 2019). "Drugmaker to seek approval for Alzheimer's treatment". CNN. Retrieved 23 October 2019.
  25. ^ McNamara, Damien (28 May 2020). "Mixed Results for Aducanumab in Two Phase 3 AD Trials". Medscape.
  26. ^ Herper M (22 October 2019). "In shocking reversal, Biogen to submit Alzheimer's drug for approval". STAT. Retrieved 22 October 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.
  27. ^ "Biogen Plans Regulatory Filing for Aducanumab in Alzheimer's Disease Based on New Analysis of Larger Dataset from Phase 3 Studies". Biogen. 22 October 2019. Retrieved 22 October 2019.

External links

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