Etranacogene dezaparvovec API Manufacturers

General Description:

Etranacogene dezaparvovec, identified by CAS number 2156583-26-3, is a notable compound with significant therapeutic applications. Hemophilia B - also called factor IX deficiency or Christmas disease - is an X-linked genetic disorder resulting in an absence or deficiency of clotting factor IX. Clotting factors, including factor IX, are necessary components of the signaling cascade responsible for blood clotting and subsequent wound healing. Symptoms of hemophilia B, therefore, involve a heightened susceptibility to bleeding episodes - in mild cases, bleeding may only occur after injury, while in more severe cases bleeding may occur after a minor injury or even spontaneously. Hemophilia B is the second most common type of hemophilia, with a prevalence of approximately one in 40,000. Men are most likely to experience symptomatic illness due to the X-linked provenance of the disorder. Treatment of hemophilia B primarily involves the routine replacement of factor IX using recombinant or donor-derived factor IX products that, while effective, may be burdensome for the patient due to the requirement of routine intravenous infusions. Etranacogene dezaparvovec (Hemgenix, CSL Bering LLC) is a gene therapy for the treatment of hemophilia B that provides a new treatment modality for its patients. The therapy involves a one-time infusion of a viral vector carrying a codon-optimized DNA sequence of the gain-of-function Padua variant of human Factor IX controlled by a liver-specific promotor 1. It delivers a copy of the deficient gene that results in cell transduction and an eventual increase in circulating factor IX activity. Etranacogene dezaparvovec was approved by the FDA in November 2022 for the treatment of select patients with hemophilia B, becoming the first gene therapy approved for this indication. It is additionally notable for its cost per treatment - approximately 3.5 million USD - earning it the title of most expensive drug in the world.

Indications:

This drug is primarily indicated for: Etranacogene dezaparvovec (Hemgenix) is indicated for the treatment of adults with hemophilia B who fit one of the following criteria: - Currently use factor IX prophylaxis therapy - Have current or historical life-threatening hemorrhage - Have repeated, serious spontaneous bleeding episodes. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Volume of Distribution:

Etranacogene dezaparvovec is distributed throughout the body with a volume of distribution of: In a study to evaluate the biodistribution of etranacogene dezaparvovec in male mice and non-human primates, the highest levels of vector DNA were detected in the liver and adrenal glands, although it was also detected in all reproductive tissues examined. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Etranacogene dezaparvovec is a critical factor in determining its safe and effective dosage: In a clinical study, the maximum time to clearance of vector DNA was 22 weeks for urine, 26 weeks for saliva and nasal secretions, 40 weeks for feces, 52 weeks for semen, and 159 weeks for blood. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Etranacogene dezaparvovec exerts its therapeutic effects through: Following a single intravenous infusion, median factor IX activity increased to 23.7% of normal by week 3, 33.8% at 3 months, 37.3% at 6 months, and peaked at 39.9% at 12 months. After 24 months, median activity remained at 33.9% of normal. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Etranacogene dezaparvovec functions by: Etranacogene dezaparvovec is a non-replicating recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized DNA sequence of the gain-of-function Padua variant of human Factor IX (variant R338L) controlled by a liver-specific promotor 1. It is administered by a single intravenous infusion and delivers a copy of the gene in which hemophilia B patients are defective, leading to cell transduction and an eventual increase in circulating activity levels of factor IX. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Categories:

Etranacogene dezaparvovec is categorized under the following therapeutic classes: Adeno-associated Viral Vector Therapies, Cellular and Gene Therapy. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.