Faricimab

Faricimab is used for: Neovascular (Wet) Age-Related Macular Degeneration (nAMD), Diabetic Macular Edema (DME), Macular Edema Following Retinal Vein Occlusion (RVO)

Intravitreal injection Faricimab is a vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor Neovascular (Wet) Age-Related Macular Degeneration (nAMD) The recommended dose for Faricimab is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to inform whether to give a 6 mg dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; 2) Weeks 24, 36 and 48; or 3) Weeks 20, 28, 36 and 44. Although additional efficacy was not demonstrated in most patients when Faricimab was dosed every 4 weeks compared to every 8 weeks, some patients may need every 4 weeks (monthly) dosing after the first 4 doses. Patients should be assessed regularly. Diabetic Macular Edema (DME) Faricimab is recommended to be dosed by following one of these two dose regimens: 1) 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days ± 7 days, monthly) for at least 4 doses. If after at least 4 doses, resolution of edema based on the central subfield thickness(CST) of the macula as measured by optical coherence tomography is achieved, then the interval of dosing may be modified by extensions of up to 4-week interval increments or reductions of up to 8-week interval increments based on CST and visual acuity evaluations; or 2) 6 mg dose of Faricimab can be administered every 4 weeks for the first 6 doses, followed by 6 mg dose via intravitreal injection at intervals of every 8 weeks (2 months). Although additional efficacy was not demonstrated in most patients when Faricimab was dosed every 4 weeks compared to every 8 weeks, some patients may need every 4 week (monthly) dosing after the first 4 doses. Patients should be assessed regularly. Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for Faricimab is 6 mg (0.05 mL of 120 mg/mL) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for 6 months.

Renal impairment Mild-to-moderate (CrCl 15-89 mL/min/1.73 m2): No dosage adjustment necessary Severe: Pharmacokinetics unknown

Intravitreal Preparation Remove vial/prefilled syringe from refrigerator and allow it to reach room temperature (20-25ºC [68-77ºF]) before administering May keep vial/prefilled syringe at room temperature for up to 24 hr; keep vial in original carton to protect from light Visually inspect vial/prefilled syringe for particulate matter and discoloration before administering; solution is clear to opalescent and colorless to brownish-yellow; discard if particulates, cloudiness, or discoloration are visible; do not use if packaging, vial, and/or transfer filter needle are expired, damaged, or have been tampered with Use aseptic technique to prepare intravitreal injection Intravitreal Administration Must be administered by qualified physician Use aseptic conditions for intravitreal injection, including use of surgical hand disinfection, sterile gloves, a sterile drape, a sterile eyelid speculum (or equivalent), and availability of sterile paracentesis equipment (if required) Administer adequate anesthesia and a broad-spectrum microbicide before injecting Slowly inject until rubber stopper reaches end of syringe to deliver 0.05 mL; confirm full dose was delivered by checking that the rubber stopper has reached end of syringe barrel; discard any unused medicinal product or waste materials in accordance with local regulations Monitor for elevated intraocular pressure immediately following intravitreal injection Appropriate monitoring may consist of a check for perfusion of optic nerve head or tonometry; if required, a sterile paracentesis needle should be available Following intravitreal injection, instruct patients to report any symptoms suggestive of endophthalmitis or retinal detachment (eg, vision loss, eye pain, eye redness, photophobia, blurred vision) without delay Each syringe should only be used for treatment of a single eye If contralateral eye requires treatment, use a new syringe, and change sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles before administering to other eye

Ocular or periocular infection Active intraocular inflammation Hypersensitivity

Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management. Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. There is a potential risk of arterial thromboembolic events (ATEs) associated with VEGF inhibition.

Pregnancy There are no adequate and well-controlled studies on use in pregnant females Do not use during pregnancy unless potential benefit to patient outweighs potential risk of fetus Contraception Females of reproductive potential: Use effective contraception before initiating, during treatment, and for ?3 months following last dose Infertility No studies conducted and unknown whether faricimab can affect reproduction capacity Based on mechanism of action, treatment may pose a risk to reproductive capacity Animal data IV administration to pregnant monkeys during organogenesis resulted in an increased incidence of abortions at doses 158x the human exposure Based on mechanism of action of VEGF and angiopoietin-2 (Ang-2) inhibitors, there is potential risks to female reproductive capacity and embryofetal development Lactation There is no information regarding presence of faricimab in human milk, its effects on breastfed infants, or its effects on milk production Many drugs are transferred in human milk with potential for absorption and adverse reactions in breastfed children

Side effects of Faricimab : 1-10% ARMD Conjunctival hemorrhage (7%) Vitreous floaters (3%) Retinal pigment epithelial tear (3%) Intraocular pressure increased (3%) Eye pain (3%) Intraocular inflammation (2%) Eye irritation (1%) Ocular discomfort (1%) DME Conjunctival hemorrhage (7%) Vitreous floaters (3%) Intraocular pressure increased (3%) Eye pain (2%) Intraocular inflammation (1%) Eye irritation (1%) Ocular discomfort (1%) Vitreous hemorrhage (1%) <1% Corneal abrasion Eye pruritus Lacrimation increased Ocular hyperemia Blurred vision Eye irritation Sensation of foreign body Endophthalmitis Visual acuity reduced transiently Retinal tear Rhegmatogenous retinal detachment ARMD Vitreous hemorrhage (<1%)

Humanized bispecific immunoglobulin G1 (IgG1) antibody binds to both vascular endothelial growth factor A (VEGF-A) and Ang-2 By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization, and vascular permeability By inhibiting Ang-2, faricimab is believed to promote vascular stability and desensitize blood vessels to the effects of VEGF-A; some nARMD and DME patients have an increase in Ang-2 levels