Aducanumab API Manufacturers

General Description:

Aducanumab, identified by CAS number 1384260-65-4, is a notable compound with significant therapeutic applications. Aducanumab, or BIIB037, is a monoclonal IgG1 antibody that targets extracellular amyloid-β plaques in the brain; similar to , and . Aducanumab is a recombinant antibody derived from patients with slow or absent cognitive decline, and phase 1b clinical trial data have shown patients treated with aducanumab show a reduction in amyloid-β plaques. Based on Mini-Mental State Examination and Clinical Dementia Rating (CDR), patients taking aducanumab showed signs of slowing progression, however, these data are controversial. 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. Although aducanumab's approval represents the first drug treatment for Alzheimer's disease, the approval is conditional on further results. 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. 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 a reanalysis of the data. Aducanumab was granted accelerated FDA approval on 7 June 2021. Continued approval will be based on further trials confirming a clinical benefit over currently available therapy.

Indications:

This drug is primarily indicated for: Aducanumab is indicated in the treatment of Alzheimer's disease. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Aducanumab undergoes metabolic processing primarily in: Aducanumab is expected to be broken down into smaller oligopeptides and amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Aducanumab are crucial for its therapeutic efficacy: A 10 mg/kg intravenous dose of aducanumab reached a C_max of 182.7 µg/mL, with a T_max of 3.0 hours, and an AUC_inf of 31,400 h\*µg/mL. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Aducanumab is an important consideration for its dosing schedule: The terminal half life of aducanumab is 24.8 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Aducanumab from the body primarily occurs through: Monoclonal IgG is predominantly eliminated by catabolism to individual amino acids that are either recycled in the body or metabolized for energy. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Aducanumab is distributed throughout the body with a volume of distribution of: The volume of distribution of aducanumab is 9.63 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Aducanumab is a critical factor in determining its safe and effective dosage: A 10 mg/kg intravenous dose of aducanumab has a clearance of 0.39 mL/h/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Aducanumab exerts its therapeutic effects through: Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β, reducing amyloid plaques in the brain. It has a long duration of action as it is given once every 4 weeks. Patients should be counselled regarding the risk of amyloid related imaging abnormalities, including microhemorrhages, and hypersensitivity reactions. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Aducanumab functions by: Alzheimer's disease is a neurodegenerative disease. Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain. These plaques are mostly composed of amyloid-β, a peptide of varying length formed by the cleavage of the amyloid precursor protein. The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-β oligopeptides in the brain drives the pathogenesis of Alzheimer's disease. Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β at amino acids 3-7. The amyloid-β residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-β and aducanumab's Fab region. Data from studies in mice and humans shows aducanumab treatment reduces amyloid-β, however human trials show non-significant changes in amyloid-β40 and amyloid-β42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-β40 and amyloid-β42 at 60 mg/kg. 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Aducanumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Aducanumab is categorized under the following therapeutic classes: Alzheimer Disease, drug therapy, Amino Acids, Peptides, and Proteins, Amyloid Beta-directed Antibodies, Anti-Dementia Drugs, Antibodies, Antibodies, Monoclonal, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Nervous System, Proteins, Psychoanaleptics, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Aducanumab include:

• Molecular Weight: 146000.0