Vabysmo (Faricimab): Uses, Dosage, Side Effects & Warnings

Q: Who makes Vabysmo?

Vabysmo is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..

Uses

1 INDICATIONS AND USAGE VABYSMO is a vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2) inhibitor indicated for the treatment of patients with: VABYSMO is a vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (nAMD) ( 1.1 ) Diabetic Macular Edema (DME) ( 1.2 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.3 ) 1.1 Neovascular (wet) Age-Related Macular Degeneration (nAMD) 1.2 Diabetic Macular Edema (DME) 1.3 Macular Edema Following Retinal Vein Occlusion (RVO)

Dosage and administration

For intravitreal injection. ( 2.1 ) Neovascular (Wet) Age-Related Macular Degeneration (nAMD) The recommended dose for VABYSMO 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 VABYSMO 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. ( 2.2 ) Diabetic Macular Edema (DME) VABYSMO 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 VABYSMO 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 VABYSMO 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. ( 2.3 ) Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for VABYSMO is 6 mg (0.05 mL of 120 mg/mL) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly). ( 2.4 ) 2.1 General Dosing Information For intravitreal injection. VABYSMO must be administered by a qualified physician. VABYSMO is available as: Prefilled syringe: A sterile injection filter needle (30-gauge × ½-inch, Extra Thin Wall) with an integrated filter in the hub is provided. Each prefilled syringe should only be used for the treatment of a single eye. Vial: A sterile 5-micron, blunt transfer filter needle (18-gauge × 1½-inch) is provided. Each vial should only be used for the treatment of a single eye. [see How Supplied/Storage and Handling (16) ] 2.2 Neovascular (wet) Age-Related Macular Degeneration (nAMD) The recommended dose for VABYSMO 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 VABYSMO 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. 2.3 Diabetic Macular Edema (DME) VABYSMO 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 VABYSMO 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 VABYSMO 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. 2.4 Macular Edema Following Retinal Vein Occlusion (RVO) The recommended dose for VABYSMO is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly). In clinical studies, patients received monthly injections of VABYSMO for 6 months [see Clinical Studies (14.3) ] . 2.5 Preparation for Administration - Prefilled Syringe Before you start Read all the instructions carefully before using VABYSMO. The VABYSMO carton includes: A sterile prefilled syringe in a sealed tray. The prefilled syringe is for treatment of a single eye. A sterile injection filter needle (30-gauge × ½ inch, Extra Thin Wall) with an integrated filter in the hub. The injection filter needle is for single use only. Only use the provided injection filter needle for the administration. VABYSMO should be refrigerated at temperatures between 2°C to 8°C (36°F to 46°F). Do not freeze. Allow VABYSMO to reach room temperature, 20°C to 25°C (68°F to 77°F) before proceeding with the administration. Prior to use, keep the sealed tray in the original carton to protect the prefilled syringe from light . The prefilled syringe may be kept at room temperature in the original carton for up to 24 hours . VABYSMO should be inspected visually prior to administration. Do not use if the carton seals have been tampered with. Do not use if the packaging, prefilled syringe, injection filter needle is expired, damaged, or have been tampered with.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS VABYSMO is a clear to opalescent, colorless to brownish-yellow solution available as: Injection: 6 mg (0.05 mL of 120 mg/mL solution) in a single-dose prefilled glass syringe Injection: 6 mg (0.05 mL of 120 mg/mL solution) in a single-dose glass vial Injection: 6 mg (0.05 mL of 120 mg/mL solution) in a single-dose prefilled syringe ( 3 ) Injection: 6 mg (0.05 mL of 120 mg/mL solution) in a single-dose vial ( 3 )

Contraindications

Ocular or periocular infection ( 4.1 ) Active intraocular inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections VABYSMO is contraindicated in patients with ocular or periocular infections. 4.2 Active Intraocular Inflammation VABYSMO is contraindicated in patients with active intraocular inflammation. 4.3 Hypersensitivity VABYSMO is contraindicated in patients with known hypersensitivity to faricimab or any of the excipients in VABYSMO. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.

Warnings and precautions

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. ( 5.1 ) Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. ( 5.2 ) There is a potential risk of arterial thromboembolic events (ATEs) associated with VEGF inhibition. ( 5.3 ) 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections, including Vabysmo, have been associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] . Proper aseptic injection techniques must always be used when administering VABYSMO. Patients should be instructed to report any signs or symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management [see Dosage and Administration (2.6) and Patient Counseling Information (17) ]. 5.2 Increase in Intraocular Pressure Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including with VABYSMO [see Adverse Reactions (6.1) ]. IOP and the perfusion of the optic nerve head should be monitored and managed appropriately [see Dosage and Administration (2.6) ]. 5.3 Thromboembolic Events Although there was a low rate of arterial thromboembolic events (ATEs) observed in the VABYSMO clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported ATEs in the nAMD studies during the first year was 1% (7 out of 664) in patients treated with VABYSMO compared with 1% (6 out of 662) in patients treated with aflibercept [see Clinical Studies (14.1) ] . The incidence of reported ATEs in the DME studies from baseline to week 100 was 5% (64 out of 1,262) in patients treated with VABYSMO compared with 5% (32 out of 625) in patients treated with aflibercept [see Clinical Studies (14.2) ] . The incidence of reported ATEs in the RVO studies during the first 6 months was 1.1% (7 out of 641) in patients treated with VABYSMO compared with 1.4% (9 out of 635) in patients treated with aflibercept [see Clinical Studies (14.3) ] . 5.4 Retinal Vasculitis and/or Retinal Vascular Occlusion Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of VABYSMO [see Adverse Reactions (6.2) ] . Discontinue treatment with VABYSMO in patients who develop these events. Patients should be instructed to report any change in vision without delay.

Side effects

The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4) ] Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.3) ] Retinal Vasculitis and/or Retinal Vascular Occlusion [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥ 5%) reported in patients receiving VABYSMO were cataract (15%) and conjunctival hemorrhage (8%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice. The data described below reflect exposure to VABYSMO in 2,567 patients, which constituted the safety population in six Phase 3 studies [see Clinical Studies (14.1 , 14.2 , 14.3) ] . Table 1: Common Adverse Reactions (≥ 1%) Adverse Reactions VABYSMO Active Control (aflibercept) AMD N=664 DME N=1,262 RVO N=641 AMD N=662 DME N=625 RVO N=635 Cataract 3% 15% < 1% 2% 12% 1% Conjunctival hemorrhage 7% 8% 3% 8% 7% 4% Vitreous detachment 3% 5% 2% 3% 4% 2% Vitreous floaters 3% 4% 2% 2% 3% 2% Retinal pigment epithelial tear AMD only 3% 1% Intraocular pressure increased 3% 4% 1% 2% 3% 3% Eye pain 3% 3% < 1% 3% 3% < 1% Intraocular inflammation Including iridocyclitis, iritis, uveitis, vitritis 2% 1% 1% 1% 1% < 1% Eye irritation 1% < 1% < 1% < 1% 1% < 1% Lacrimation increased 1% 1% 0 1% < 1% < 1% Ocular discomfort 1% 1% < 1% < 1% < 1% < 1% Less common adverse reactions reported in < 1% of the patients treated with VABYSMO were corneal abrasion, eye pruritus, ocular hyperemia, blurred vision, sensation of foreign body, endophthalmitis, conjunctival hyperaemia, visual acuity reduced, visual acuity reduced transiently, vitreous hemorrhage, retinal tear and rhegmatogenous retinal detachment. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of VABYSMO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : retinal vasculitis with or without retinal vascular occlusion.

Use in specific populations

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of VABYSMO administration in pregnant women. Administration of VABYSMO to pregnant monkeys throughout the period of organogenesis resulted in an increased incidence of abortions at intravenous (IV) doses 158 times the human exposure (based on C max ) of the maximum recommended human dose [see Animal Data ] . Based on the mechanism of action of VEGF and Ang-2 inhibitors, there is a potential risk to female reproductive capacity, and to embryo-fetal development. VABYSMO should not be used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. All pregnancies have a background risk of birth defect, loss, and other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. Data Animal Data An embryo fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received 5 weekly IV injections of VABYSMO starting on day 20 of gestation at 1 or 3 mg/kg. A non-dose dependent increase in pregnancy loss (abortions) was observed at both doses evaluated. Serum exposure (C max ) in pregnant monkeys at the low dose of 1 mg/kg was 158 times the human exposure at the maximum recommended intravitreal dose of 6 mg once every 4 weeks. A no observed adverse effect level (NOAEL) was not identified in this study. 8.2 Lactation Risk Summary There is no information regarding the presence of faricimab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Many drugs are transferred in human milk with the potential for absorption and adverse reactions in the breastfed child. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VABYSMO and any potential adverse effects on the breastfed child from VABYSMO. 8.3 Females and Males of Reproductive Potential Contraception Females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment and for at least 3 months following the last dose of VABYSMO. Infertility No studies on the effects of faricimab on human fertility have been conducted and it is not known whether faricimab can affect reproduction capacity. Based on the mechanism of action, treatment with VABYSMO may pose a risk to reproductive capacity. 8.4 Pediatric Use The safety and efficacy of VABYSMO in pediatric patients have not been established. 8.5 Geriatric Use In the six clinical studies, approximately 58% (1,496/2,571) of patients randomized to treatment with VABYSMO were ≥ 65 years of age. No significant differences in efficacy or safety of faricimab were seen with increasing age in these studies. No dose adjustment is required in patients 65 years and above.

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of VABYSMO administration in pregnant women. Administration of VABYSMO to pregnant monkeys throughout the period of organogenesis resulted in an increased incidence of abortions at intravenous (IV) doses 158 times the human exposure (based on C max ) of the maximum recommended human dose [see Animal Data ] . Based on the mechanism of action of VEGF and Ang-2 inhibitors, there is a potential risk to female reproductive capacity, and to embryo-fetal development. VABYSMO should not be used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. All pregnancies have a background risk of birth defect, loss, and other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. Data Animal Data An embryo fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received 5 weekly IV injections of VABYSMO starting on day 20 of gestation at 1 or 3 mg/kg. A non-dose dependent increase in pregnancy loss (abortions) was observed at both doses evaluated. Serum exposure (C max ) in pregnant monkeys at the low dose of 1 mg/kg was 158 times the human exposure at the maximum recommended intravitreal dose of 6 mg once every 4 weeks. A no observed adverse effect level (NOAEL) was not identified in this study.

Pediatric use

8.4 Pediatric Use The safety and efficacy of VABYSMO in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use In the six clinical studies, approximately 58% (1,496/2,571) of patients randomized to treatment with VABYSMO were ≥ 65 years of age. No significant differences in efficacy or safety of faricimab were seen with increasing age in these studies. No dose adjustment is required in patients 65 years and above.

Description

Faricimab-svoa is a humanized bispecific immunoglobulin G1 (IgG1) antibody that binds both vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). The fragment crystallizable (Fc) region of faricimab was engineered by selected point mutations to abolish binding interactions with Fcγ and FcRn receptors. Faricimab-svoa has a total molecular weight of approximately 149 kDa and is produced by recombinant DNA technology using mammalian Chinese Hamster Ovary (CHO) cell culture. VABYSMO (faricimab-svoa) injection is a sterile, clear to opalescent, colorless to brownish-yellow solution in a single-dose prefilled glass syringe or glass vial for intravitreal administration. Each single-dose prefilled syringe or single-dose vial is designed to deliver 0.05 mL (50 microliters) of solution containing 6 mg faricimab-svoa, L-histidine (155 mcg), L-methionine (52.2 mcg), polysorbate 20 (20 mcg), sodium chloride (73.1 mcg), D-sucrose (2.74 mg) and Water for Injection, adjusted to pH 5.5 with acetic acid. The product does not contain an anti-microbial preservative.

Mechanism of action

12.1 Mechanism of Action Faricimab is a humanized bispecific antibody that acts through inhibition of two pathways by binding to VEGF-A and Ang-2. By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization and vascular permeability. By inhibiting Ang-2, faricimab is thought to promote vascular stability and desensitize blood vessels to the effects of VEGF-A. Ang-2 levels are increased in some patients with nAMD, DME, and RVO. The contribution of Ang-2 inhibition to the treatment effect and clinical response for nAMD, DME, and RVO has yet to be established.

How supplied

16.1 How Supplied VABYSMO (faricimab-svoa) injection is supplied as a clear to opalescent, colorless to brownish-yellow solution as 6 mg (0.05 mL of 120 mg/mL solution) in a single-dose prefilled syringe or single-dose vial. Each prefilled syringe or vial is for treatment of a single eye. VABYSMO is supplied in the following presentations: NDC NUMBER CARTON TYPE CARTON CONTENTS 50242-096-06 Prefilled Syringe one 6 mg (0.05 mL of 120 mg/mL solution) single-dose prefilled glass syringe, in a sealed tray one sterile injection filter needle (30-gauge × ½ inch, 0.30 mm × 12.7 mm, Extra Thin Wall) one Prescribing Information 50242-096-01 Vial one 6 mg (0.05 mL of 120 mg/mL solution) single-dose glass vial one sterile 5-micron blunt transfer filter needle (18-gauge × 1½ inch, 1.2 mm × 40 mm) one Prescribing Information 16.2 Storage and Handling Store VABYSMO in the refrigerator between 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake. Keep the sealed tray containing the prefilled syringe or the vial in the original carton to protect from light. Prior to use, the unopened prefilled syringe or glass vial of VABYSMO may be kept at room temperature, 20°C to 25°C (68°F to 77°F), for up to 24 hours. Ensure that the injection is given immediately after preparation of the dose.

Storage

16.2 Storage and Handling Store VABYSMO in the refrigerator between 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake. Keep the sealed tray containing the prefilled syringe or the vial in the original carton to protect from light. Prior to use, the unopened prefilled syringe or glass vial of VABYSMO may be kept at room temperature, 20°C to 25°C (68°F to 77°F), for up to 24 hours. Ensure that the injection is given immediately after preparation of the dose.

Patient information

Advise patients that in the days following VABYSMO administration, patients are at risk of developing endophthalmitis, retinal detachment, intraocular inflammation and retinal vasculitis with or without retinal vascular occlusion. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise the patient to seek immediate care from an ophthalmologist [see Warnings and Precautions (5) ] . Patients may experience temporary visual disturbances after an intravitreal injection with VABYSMO and the associated eye examinations [see Adverse Reactions (6) ] . Advise patients not to drive or use machinery until visual function has recovered sufficiently.

Active ingredients

Faricimab in 1 product

Vabysmo NDC products (1)

NDC	Strength & form	Labeler	Type
50242-096	Faricimab 6 mg/.05mL Injection, Solution	Genentech, Inc.	BLA

Frequently asked questions

What is Vabysmo used for?

1 INDICATIONS AND USAGE VABYSMO is a vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2) inhibitor indicated for the treatment of patients with: VABYSMO is a vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (nAMD) ( 1.1 ) Diabetic Macular Edema (DME) (…

What are the side effects of Vabysmo?

The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4) ] Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.3) ] Retinal Vasculitis and/or Retinal Vascular… See the full label for the complete list.

Who makes Vabysmo?

Vabysmo is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..