Faricimab API Manufacturers

General Description:

Faricimab, identified by CAS number 1607793-29-2, is a notable compound with significant therapeutic applications. Retinal vascular diseases (RVDs) such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) are typically caused by retinal ischemia and subsequent neovascularization (NV). Vascular endothelial growth factor A (VEGF-A) is a well-known mediator of retinal NV, and many currently approved RVD therapies such as and solely target VEGF-A. However, another set of factors, the Tie/Ang axis, comprising the transmembrane Tie-2 receptor and its soluble ligands Ang-1 and Ang-2, has been shown to play critical roles in mediating VEGF-A-induced NV. Faricimab is an IgG₁-derived bispecific antibody capable of simultaneously binding to and depleting VEGF-A and Ang-2, which has been developed to improve therapeutic efficacy, especially in patients that respond poorly to anti-VEGF-A monotherapy. Faricimab was approved by the FDA on January 28, 2022, and is currently marketed under the trademark VABYSMO by Genentech, Inc. It received subsequent approval for the same indications in Canada in May 2022. In July 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended faricimab be granted marketing authorization for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

Indications:

This drug is primarily indicated for: Faricimab is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Faricimab undergoes metabolic processing primarily in: Faricimab metabolism has not been fully characterized; as an antibody, faricimab is expected to be catabolized like endogenous immunoglobulins. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Faricimab are crucial for its therapeutic efficacy: Faricimab unbound plasma C_max are estimated to be 0.23 ± 0.07 and 0.22 ± 0.07 μg/mL in nAMD and DME patients, respectively; these plasma levels are achieved approximately two days post-dose (T_max). Following repeated intravitreal administration on a q8w schedule, mean plasma trough free faricimab concentrations are predicted to be 0.002-0.003 μg/mL. No accumulation is expected in either the vitreal fluid or plasma. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Faricimab is an important consideration for its dosing schedule: Faricimab has an estimated mean apparent systemic half-life of 7.5 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Faricimab from the body primarily occurs through: Faricimab elimination has not been fully characterized; faricimab may be excreted renally following its breakdown into smaller peptides and amino acids through cellular catabolism. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Pharmacodynamics:

Faricimab exerts its therapeutic effects through: Faricimab is a bispecific antibody (bsAb) based on human IgG₁ comprising two different heavy and two different light chains capable of simultaneously binding to both VEGF-A and Ang-2. Faricimab suppresses endothelial proliferation, neovascularization, and vascular permeability, which are associated with the increased retinal thickness observed in nAMD and DME. In four phase 3 studies in nAMD and DME, faricimab reduced central subfield thickness through the first year in all treatment arms. As with other medications administered intravitreally, faricimab carries a risk of transient increases in intraocular pressure, endophthalmitis, and retinal detachment. Proper injection techniques should always be observed, and patients monitored carefully following injection. Low risk of arterial thromboembolic events, defined as nonfatal stroke or myocardial infarction and vascular death, has been documented with faricimab. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Faricimab functions by: The retina is largely avascular to facilitate effective photoreceptor function; rather, the retina is fed by both retinal and choroidal capillary networks, pathologies of which result in retinal and choroidal vascular diseases such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). One of the underlying causes of retinal vascular diseases (RVDs) is retinal neovascularization (NV), the aberrant growth of new vasculature, usually due to sustained retinal ischemia and mediated primarily by vascular endothelial growth factor A (VEGF-A). VEGF-A is a VEGF family member, which also includes VEGF-B, -C, and -D, whose members signal through the VEGF receptors (VEGFRs) VEGFR-1, -2, and -3 to mediate endothelial and lymphatic growth. Extensive work in animal models of RVD has demonstrated that VEGF-A is necessary but not sufficient in many cases to mediate NV, suggesting that additional factors may be required in deep retinal capillary beds. One such factor has been identified as the angiopoietins Ang-1 and Ang-2 and their cellular receptor Tie-2; Ang-1 is a full Tie-2 agonist whose binding results in Tie-2 phosphorylation and downstream signalling, whereas Ang-2 is a Tie-2 partial agonist/antagonist that inhibits Tie-2 phosphorylation. Ang-1 generally has a protective effect, making endothelial cells less responsive to VEGF-A, while Ang-2 increases VEGF-A-dependent NV and stimulates pericyte apoptosis and breakdown of both the blood-brain and blood-retinal barriers; Ang-2 is upregulated in retinal vascular development and retinal ischemia. Faricimab is a bispecific antibody (bsAb) based on human IgG₁ comprising two different heavy and two different light chains capable of simultaneously binding to both VEGF-A and Ang-2 produced using the "CrossMab" platform. Faricimab binds VEGF-A and Ang-2 with binding affinities (K_D) of approximately 3 and 22 nM, respectively; importantly, faricimab does not detectably bind Ang-1. Also, the faricimab Fc region has been modified to reduce binding to FcγR and FcRn receptors. The former virtually eliminates immune-mediated functions such as antibody- and complement-dependent cytotoxicity and antibody-dependent phagocytosis, whereas the latter increases faricimab systemic clearance by reducing FcRn-mediated IgG recycling. Thus, faricimab works by depleting both VEGF-A and Ang-2 to prevent retinal NV in the privileged ophthalmic environment. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Faricimab 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:

Faricimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood Proteins, Immunoglobulins, Proteins, 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 Faricimab include:

• Molecular Weight: 149000.0
• Molecular Formula: C6506H9968N1724O1026S45