Albutrepenonacog alfa API Manufacturers

General Description:

Albutrepenonacog alfa, identified by CAS number 1357448-54-4, is a notable compound with significant therapeutic applications. Albutrepenonacog alfa (rIX-RFP) is a recombinant fusion protein that links a recombinant coagulation factor IX (rFIX) with a recombinant human albumin (rAlbumin). It was developed by CSL Behring Canada, Inc and approved by Health Canada on April 26, 2017. It was also approved by FDA and EMA in 2016. It is currently marketed in the forms of 250, 500, 1000 and 2000 IU/vial.

Indications:

This drug is primarily indicated for: Under the EMA and FDA, rIX-RFP is indicated in the treatment of hemophilia B. For Health Canada, rIX-FRP is also indicated to prevent or reduce bleeding episodes. Hemophilia B is the second most common type of hemophilia. It is a rare inherited bleeding disorder caused by reduced or absent levels of factor IX (FIX). The FIX is a vitamin K-dependent plasma protease that when activated is involved in the blood coagulation cascade. The hemophilia B is caused by mutations in the _FIX_ gene which can cause different phenotypes. The severe form is characterized by the presence of spontaneous and recurring bleeds into the joints and muscles and excessive bleeding after trauma or surgery. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Albutrepenonacog alfa undergoes metabolic processing primarily in: The metabolism of rIX-RFP is not relevant as it is a recombinant protein and it is thought to be metabolized to peptides 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 Albutrepenonacog alfa are crucial for its therapeutic efficacy: rIX-RFP absorption is very rapid as it is directly administered intravenously. In clinical trials, the maximum plasma concentration, area under the curve and mean residence time are reported to be approximately 55 IU/dL, 5500 IU.h/dL and 125 hours respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Albutrepenonacog alfa is an important consideration for its dosing schedule: The fusion of the rFIX with rAlbumin prolongs the elimination half-life of rIX-RFP in the circulation. The reported half-life in clinical trials is 92 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Albutrepenonacog alfa exhibits a strong affinity for binding with plasma proteins: This pharmacokinetic value is not relevant as this drug is part of the plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Albutrepenonacog alfa from the body primarily occurs through: rIX-RFP is mainly eliminated in the urine. In preclinical studies, the distribution of urine and feces 240 hours post administration corresponded to 72.9% and 4.3% of the administered dose respectively. The elimination on the first 24 hours in urine and feces only corresponded to the 39.9% and 0.92% of the dose. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Albutrepenonacog alfa is distributed throughout the body with a volume of distribution of: The reported volume of distribution for rIX-RFP according to phase I/II and III clinical trials is 95 ml/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Albutrepenonacog alfa is a critical factor in determining its safe and effective dosage: In clinical trials, the weight-adjusted clearance in children and adults is reported to be 1.1 and 0.9 ml/h/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Albutrepenonacog alfa exerts its therapeutic effects through: Clinical trials with rIX-RFP in patients with moderately to severe hemophilia B demonstrated a lower annualized spontaneous, total and joint bleeding rates. It was also efficient against bleeding episodes and maintenance of hemostasis in the perioperative setting when compared with on-demand treatment. The administration of rIX-RFP presented no reports of inhibitor development. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Albutrepenonacog alfa functions by: The current therapies against hemophilia B are hampered by the short half-life of the replacement FIX therapy. Thus, to solve this problem, in rIX-RFP there is the fusion of rFIX with rAlbumin which presents a much longer half-life and it does not present interactions with the immune system. The administration of rIX-RFP increases the plasma concentration of FIX, thus addressing the coagulation deficiency of the patient. rIX-RFP is able to circulate in the plasma as an intact zymogen thanks to the pH-dependent binding to FcRn which is a normal protection pathway from lysosomal degradation of albumin. When the FIX is needed, rAlbumin is cleaved by the same proteases that activate the FIX. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Albutrepenonacog 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:

Albutrepenonacog alfa is categorized under the following therapeutic classes: Albumins, Amino Acids, Peptides, and Proteins, Biological Factors, Blood Coagulation Factors, Blood Proteins, Drugs that are Mainly Renally Excreted, Enzyme Precursors, Enzymes and Coenzymes, Hemostatics, Protein Precursors, Proteins, Recombinant Proteins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Albutrepenonacog alfa include:

• Molecular Weight: 125000.0
• Molecular Formula: C5077N7846O1588PS67