Efbemalenograstim alfa API Manufacturers

General Description:

Efbemalenograstim alfa, identified by CAS number 2200269-79-8, is a notable compound with significant therapeutic applications. Efbemalenograstim alfa is a long-acting recombinant fusion protein of granulocyte-colony stimulating factor (G-CSF) due to the addition of the Fc portion of human IgG2, allowing for once-per-cycle administration. As endogenous G-CSF mediates the differentiation of hematopoietic stem cells into granulocytes and eventually neutrophils, the administration of recombinant G-CSF like efbemalenograstim alfa can stimulate the production of neutrophils and thus reducing the severity and duration of neutropenia. On November 22, 2023, efbemalenograstim alfa was approved by the FDA under the brand name Ryzneuta for the treatment of chemotherapy-induced neutropenia in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. This approval was contingent on positive results observed in two pivotal Phase 3 Studies GC-627-04 and GC-627-05 in the US and Europe respectively.

Indications:

This drug is primarily indicated for: Efbemalenograstim alfa is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Efbemalenograstim alfa undergoes metabolic processing primarily in: Efbemalenograstim alfa-vuxw is expected to be metabolized into small peptides by catabolic pathways. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Efbemalenograstim alfa are crucial for its therapeutic efficacy: The median t_max of efbemalenograstim alfa-vuxw administered as 80 to 320 μg/kg in female patients with breast cancer receiving EC chemotherapy ranged from 24 hours to 48 hours in Cycle 1 and 9 to 30 hours in Cycle 3. The median t_max of efbemalenograstim alfa-vuxw administered as 240 to 320 μg/kg in female participants with breast cancer receiving TAC chemotherapy was 36 hours in Cycle 1 and ranged from 24 to 30 hours in Cycle 3. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Efbemalenograstim alfa is an important consideration for its dosing schedule: The geometric mean (CV%) elimination half-life of efbemalenograstim alfa-vuxw was 35.6 h (108%) in Cycle 1 and 36.9 h (120%) in Cycle 3. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Efbemalenograstim alfa exhibits a strong affinity for binding with plasma proteins: There is limited information on the protein binding of efbemalenograstim alfa-vuxw. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Efbemalenograstim alfa from the body primarily occurs through: Neutrophil receptor binding is an important component of the clearance of efbemalenograstim alfa-vuxw, and serum clearance is directly related to the number of neutrophils. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Efbemalenograstim alfa is distributed throughout the body with a volume of distribution of: The geometric mean (CV%) apparent volume of distribution of efbemalenograstim alfa-vuxw was 18.8 L (257%) in Cycle 1 and 40.7 L (387%) in Cycle 3 in female patients with breast cancer. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Efbemalenograstim alfa is a critical factor in determining its safe and effective dosage: The geometric mean (CV%) apparent clearance of efbemalenograstim alfa-vuxw was 0.36 L/h (110%) in Cycle 1 and 0.76 L/h (167%) in Cycle 3. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Efbemalenograstim alfa exerts its therapeutic effects through: Over the tested dose range of 30 to 360 μg/kg in healthy adult males, neutrophils generally increased in a dose-dependent manner; however, the effect on neutrophils plateaued at the top two doses of 240 and 360 μg/kg. In patients with breast cancer given EC chemotherapy, in cycle 1, median ANC peaked on Day 4 (about 24 hours after efbemalenograstim alfa-vuxw administration) for the 240 and 320 μg/kg doses, declined to nadir on Days 8–9, and then recovered to a count of 2.0 × 109/L and higher by Day 11. The ANC levels in cycles 2, 3, and 4 tended to be higher than those observed in cycle 1. In patients with breast cancer given TAC chemotherapy, in cycle 1, median ANC peaked on Day 3 (about 24 hours after efbemalenograstim alfa-vuxw administration) in cycle 1 and 3, reached nadir on Day 8, and recovered to 2.0 x 109/L on Days 9 and 10 for the 320 μg/kg and 240 μg/kg doses, respectively. Mean ANC nadir was higher with 320 μg/kg compared to 240 μg/kg in both cycle 1 (0.75 x 109/L and 0.29 x 109/L, respectively), and cycle 3 (1.19 x 109/L and 0.57 x 109/L, respectively). The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Efbemalenograstim alfa functions by: Efbemalenograstim alfa-vuxw is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end-cell functional activation. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Efbemalenograstim 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:

Efbemalenograstim alfa is categorized under the following therapeutic classes: Adjuvants, Immunologic, Antineoplastic and Immunomodulating Agents, Colony-Stimulating Factors, Granulocyte Colony-Stimulating Factors, Leukocyte Growth Factor. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.