Faricimab

Breast Feeding; Lactation; Milk, Human; Antibodies, Monoclonal; Angiogenesis Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

S - Sensory organs

QS - Sensory organs

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 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.