Velmanase alfa API Manufacturers

General Description:

Velmanase alfa, identified by CAS number 1492823-75-2, is a notable compound with significant therapeutic applications. Velmanase alfa is a recombinant human lysosomal alpha-mannosidase developed for enzyme replacement therapy to treat alpha-mannosidosis. Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder. Patients with alpha-mannosidosis have a genetic mutation that causes a deficiency in the lysosomal enzyme alpha-mannosidase, which is an enzyme responsible for breaking down complex sugars in the body. The resulting accumulation of sugars in the body leads to an array of clinical manifestations leading to progressive neuromuscular and skeletal deterioration, such as skeletal abnormalities, motor function impairment, intellectual disability, and respiratory dysfunction. As long-term enzyme replacement therapy, velmanase alfa intends to supplement or restore the function of deficient alpha-mannosidase. Velmanase alfa has an amino acid sequence of the monomeric protein identical to the naturally occurring human alpha-mannosidase. It was granted marketing authorization by the European Commission in March 2018 under the market name Lamzede as the first human recombinant form of alpha-mannosidase. It is currently not approved in the United States or Canada.

Indications:

This drug is primarily indicated for: Velmanase alfa is an enzyme replacement therapy for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Velmanase alfa undergoes metabolic processing primarily in: Velmanase alfa is expected to undergo nonspecific degradation into small peptides and subsequently amino acids, similar to other natural occurring proteins. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Velmanase alfa are crucial for its therapeutic efficacy: Following weekly intravenous infusion of 1 mg/kg of velmanase alfa, the mean C_max of 8 µg/mL at steady-state was reached at 1.8 hours after the start of administration. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Velmanase alfa is an important consideration for its dosing schedule: At the end of intravenous infusion, velmanase alfa plasma concentrations fell in a biphasic fashion with a mean terminal elimination half-life of about 30 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Velmanase alfa exhibits a strong affinity for binding with plasma proteins: There is no information. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Velmanase alfa from the body primarily occurs through: There is no information. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Velmanase alfa is distributed throughout the body with a volume of distribution of: The steady-state volume of distribution is 0.27 L/kg, indicating distribution confined to plasma. It does not cross the blood-brain barrier. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Velmanase alfa is a critical factor in determining its safe and effective dosage: The mean clearance of velmanase alfa from plasma is 6.7 mL/h/kg: it is consistent with rapid cellular uptake of velmanase alfa via mannose receptors. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Velmanase alfa exerts its therapeutic effects through: Velmanase alfa is an enzyme replacement therapy that aims to reduce oligosaccharide levels in patients with alpha-mannosidosis. In clinical trials, reduced serum oligosaccharide levels and improvements in biochemical and functional measures were seen at 18 months and for up to four years of treatment. Reversing the organ damage or showing improvements in alpha-mannosidosis becomes increasingly difficult as the accumulation of end-organ damage progresses over time. Velmanase alfa has no effects on irreversible complications of the disorder, such as skeletal deformities, dysostosis multiplex, neurological manifestations, and impaired cognitive function. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Velmanase alfa functions by: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder: it is a multi-systemic disease, characterized by a wide range of clinical manifestations including skeletal abnormalities, motor function impairment, intellectual disability, hearing loss, respiratory dysfunction, recurrent infections, and immunodeficiency usually presenting in early childhood. Alpha-mannosidosis is caused by pathogenic sequence variants in the MAN2B1 gene, leading to the deficiency of the lysosomal enzyme, alpha-mannosidase. Alpha-mannosidase is a lysosomal enzyme involved in glycoprotein catabolism. Deficient alpha-mannosidase results in the accumulation of mannose-rich oligosaccharides, causing impaired cellular function and apoptosis in all tissues. Velmanase alfa is a recombinant form of human alpha-mannosidase. Upon administration, velmanase alfa supplements or replaces natural alpha-mannosidase to properly break down hybrid and complex high-mannose oligosaccharides in the lysosome, reducing the amount of accumulated mannose-rich oligosaccharides. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Velmanase alfa 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:

Velmanase alfa is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Enzyme Replacement Therapy, Enzymes, Enzymes and Coenzymes. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.