Aducanumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | beta amyloid |
| Clinical data | |
| Other names | BIIB037 |
| ATC code |
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| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6472H10028N1740O2014S46 |
| Molar mass | 145909 g·mol−1 |
Aducanumab is a human monoclonal antibody that has been studied for the treatment of Alzheimer's disease (AD).[2] It was developed by Biogen Inc., which licensed the drug candidate from Neurimmune, its discoverer.[3] 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.[4] 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.[5][6][7]
On 22 October 2019 Biogen announced that it would be restarting the FDA approval process for aducanumab stating that new analysis of a larger dataset showed that the drug reduced clinical decline in patients with early Alzheimer's disease when given at higher doses.[8] In the EMERGE trial patients receiving a high dose had a significant reduction in their rate of decline (23% versus placebo) but the identical ENGAGE trial did not show a significant reduction with a decline only 2% slower than in the placebo group.[9][10][11] 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. The FDA's final decision whether to greenlight the drug is expected by March 2021.[12]
Research
Interim results from the second Phase I study of the drug were reported in March 2015.[2][13]
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.[14] Phase 3 clinical trials were ongoing in September 2016,[14] but were canceled in March 2019 after "an independent group's analysis show[ed] that the trials were unlikely to 'meet their primary endpoint.'"[15]
Despite this, in October 2019 the company announced their intention to seek regulatory approval, following a reanalysis of the data.[16][17][18] An independent advisory panel suggested that the FDA not approve aducanumab on November 6th 2020, citing questionable efficacy and multiple “red flags” found with the data analysis.[19]
References
- ^ "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 Oct 2023.
- ^ a b 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.
- ^ Zacks R (November 20, 2007). "Biogen Inks $380 Million Deal with Swiss Company". Xconomy.
- ^ 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.
- ^ Ducharme J (March 21, 2019). "Biogen Halts Promising Alzheimer's Drug Trials Due to Disappointing Results". Time. Retrieved 2019-03-21.
- ^ Li Y (March 21, 2019). "Biogen posts its the worst day in 14 years after ending trial for blockbuster Alzheimer's drug". CNBC.
- ^ Annett T. "Biogen Plunges More Than 25 Percent on Alzheimer's Setback". Bloomberg News.
- ^ Howard J, Gumbrecht J (October 23, 2019). "Drugmaker to seek approval for Alzheimer's treatment". CNN. Retrieved October 23, 2019.
- ^ McNamara, Damien (May 28, 2020). "Mixed Results for Aducanumab in Two Phase 3 AD Trials". Medscape.
- ^ 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.
- ^ "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.
- ^ "FDA panel rejects Biogen's new Alzheimer's drug". NBC News. 6 November 2020. Retrieved 16 December 2020.
- ^ Herper M (March 20, 2015). "Biogen Drug Could Inspire New Hope For Alzheimer's Treatments". Forbes.
- ^ 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.
- ^ Li Y (21 March 2019). "Biogen shares plunge nearly 30% after ending trial for Alzheimer's drug Aducanumab". CNBC.
- ^ Roberts M (22 October 2019). "First drug to slow Alzheimer's may be available soon". BBC News. Retrieved 22 October 2019.
- ^ Foster L (October 26, 2019). "Drug 'could be biggest Alzheimer's development'". BBC News. Retrieved October 26, 2019.
- ^ Kunkle F (December 6, 2019). "Biogen's potential new drug for Alzheimer's disease gets cautiously optimistic review following presentation". The Washington Post.
- ^ Marchione, Marilynn; Perrone, Matthew (November 8, 2020). "FDA panel urges rejection of experimental Alzheimer's drug". Associated Press on MSNBC.