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| Primary information |
|---|
| ID | 14251 |
| Therapeutic ID | Th1480 |
| Protein Name | Aducanumab |
| Sequence | >Th1480_Aducanumab
XVQLVESGGGVVQPGRSLRLSCAASGFAFSSYGMHWVRQAPGKGLEWVAVIWFDGTKKYYTDSVKGRFTISRDNSKNTLYLQMNTLRAEDTAVYYCARDRGIGARRGPYYMDVWGKGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
|
| Molecular Weight | 146000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal half life of aducanumab is 24.8 days.[L34393] |
| Description | Aducanumab, or BIIB037, is a monoclonal IgG1 antibody that targets extracellular amyloid-ß plaques in the brain; similar to [gantenerumab], [bapineuzumab] and [solanezumab].[A235668,A235730] Aducanumab is a recombinant antibody derived from patients with slow or absent cognitive decline, and phase 1b clinical trial data has shown patients treated with aducanumab show a reduction in amyloid-ß plaques.[A235668] Based on Mini-Mental State Examination and Clinical Dementia Rating (CDR), patients taking aducanumab showed signs of slowing progression, however these data are controversial.[A235668,A235720] Clinical trials showed a 23% relative difference between the experimental and placebo groups as determined by CDR, however this is equivalent to an absolute difference of 0.4/18.[A235720] Although aducanumab's approval represents the first drug treatment for Alzheimer's disease, the approval is conditional on further results.[L34420] Biogen enrolled patients in phase 3 clinical trials in 2015, but increased the size of the trials from 1350 patients to 1650 patients to maintain statistical power in the face of a high standard deviation.[A235720] Development of aducanumab was discontinued in March 2019 when two phase 3 clinical trials did not pass futility analysis, however Biogen sought FDA approval in October 2019 after reanalysis of the data.[A235720] Aducanumab was granted accelerated FDA approval on 7 June 2021.[L34393] Continued approval will be based on further trials confirming a clinical benefit over currently available therapy.[L34420] |
| Indication/Disease | Aducanumab is indicated in the treatment of Alzheimer's disease.[L34393] |
| Pharmacodynamics | Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-ß, reducing amyloid plaques in the brain.[L34393] It has a long duration of action as it is given once every 4 weeks.[L34393] Patients should be counselled regarding the risk of amyloid related imaging abnormalities, including microhemorrhages, and hypersensitivity reactions.[L34393] |
| Mechanism of Action | Alzheimer's disease is a neurodegenerative disease.[A235668] Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain.[A235668] These plaques are mostly composed of amyloid-ß, a peptide of varying length formed by the cleavage of the amyloid precursor protein.[A235668] The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-ß oligopeptides in the brain drives the pathogenesis of Alzheimer's disease.[A235730] Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-ß at amino acids 3-7.[A235668,L34393] The amyloid-ß residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-ß and aducanumab's Fab region.[A235668] Data from studies in mice and humans shows aducanumab treatment reduces amyloid-ß, however human trials show non-significant changes in amyloid-ß40 and amyloid-ß42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-ß40 and amyloid-ß42 at 60 mg/kg.[A235730] Aducanumab treatment is associated with slowing the rate of progression of Alzheimer's disease, based on Mini-Mental State Examination, Clinical Dementia Rating, and levels of p-tau in the cerebrospinal fluid.[A235715] |
| Toxicity | Patients experiencing dose-limiting toxicity may present with amyloid-related imaging abnormalities including edema or microhemorrhages of the brain.[A235730] Symptoms of dose limiting toxicity were generally transient,[A235730] however patients may need to be treated with symptomatic and supportive measures. |
| Metabolism | Aducanumab is expected to be broken down into smaller oligopeptides and amino acids.[A40006,L34393] |
| Absorption | A 10 mg/kg intravenous dose of aducanumab reached a Cmax of 182.7 µg/mL, with a Tmax of 3.0 hours, and an AUCinf of 31,400 h |
| The volume of distribution of aducanumab is 9.63 L.[L34393] |
| Clearance | A 10 mg/kg intravenous dose of aducanumab has a clearance of 0.39 mL/h/kg.[A235730] |
| Categories | Antibodies, Monoclonal |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Amyloid beta A4 protein |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |