BRIEF SUMMARY

FARICIMAB-(Jan 2022)

Indcn- To treat  neovascular (wet) aged related macular                                                            degeneration and diabetic macular edema       

Dosage- 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 

ADR- The most common adverse reaction (= 5%) reported in patients receiving VABYSMO was conjunctival hemorrhage (7%). 

CI- Ocular or periocular infection. Active intraocular inflammation .  Hypersensitivity

WARNINGS- 

 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 intravitrealevaluations 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.

Pat Inform-

Advise patients that in the days following drug  administration, patients are at risk of developing endophthalmitis.

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

Patients may experience temporary visual disturbances after an intravitreal injection with VABYSMO and the associated eye examinations

 Advise patients not to drive or use machinery until visual function has recovered sufficiently.

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U.S. FDA APPROVED DRUGS SURING 2022                                        

Serial No 4

Name of the Drug-    VABYSMO

Active Ingredient -   Faricimabsvoa

Pharmacological Classification- To treat  neovascular (wet) aged related macular                                                            degeneration and diabetic macular edema                                                                                                                                                                                                                                                                                             

Date of Approval-          1/28//22   

HIGHLIGHTS OF PRESCRIBING INFORMATION-                                                           These highlights do not include all the information needed to use VABYSMO safely and effectively.                                                                                                                      See full prescribing information for VABYSMO. VABYSMO™ (faricimab-svoa) injection, for intravitreal use

Initial U.S. Approval: 2022

INDICATIONS AND USAGE

 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)

 Diabetic Macular Edema (DME)

ADVERSE REACTIONS-

 The most common adverse reaction (= 5%) reported in patients receiving VABYSMO was conjunctival hemorrhage (7%). 

CONTRAINDICATIONS

Ocular or periocular infection

 Active intraocular inflammation .  Hypersensitivity

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.

 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.

DOSAGE AND ADMINISTRATION-

 For intravitreal injection.                                                                                         Neovascular (Wet) Age-Related Macular Degeneration (nAMD)                                     

o 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.

 Diabetic Macular Edema (DME)                                                                                      o 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 through week 52; 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) over the next 28 weeks.

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.

DOSAGE FORMS AND STRENGTHS                                                                  Injection: 120 mg/mL solution in a single-dose vial

PATIENT COUNSELING INFORMATION -

Advise patients that in the days following VABYSMO administration, patients are at risk of developing endophthalmitis.

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

Patients may experience temporary visual disturbances after an intravitreal injection with VABYSMO and the associated eye examinations

 Advise patients not to drive or use machinery until visual function has recovered sufficiently.

VABYSMO™ [faricimab-svoa] Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 U.S. License No.: 1048

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                           Faricimab is a humanized bispecific antibody that acts through inhibition of two pathways by binding to VEGF-A and Ang-

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 and DME.

The contribution of Ang-2 inhibition to the treatment effect and clinical response for nAMD and DME has yet to be established.

2. Pharmacodynamics-                                                                                      Increased retinal thickness, assessed by optical coherence tomography (OCT), is associated with nAMD and DME. Leakage of blood and fluid from choroidal neovascularization, assessed by fluorescein angiography, is associated with nAMD.

Reductions in central subfield thickness (CST) were observed from baseline through the first year of treatment across all treatment arms in the four Phase 3 studies in nAMD and DME.

3. Pharmacokinetics

Absorption/Distribution-                                                                                          Maximum faricimab plasma concentrations (Cmax) are estimated to occur approximately 2 days post-dose. Mean (±SD) free faricimab (unbound to VEGF-A and Ang-2) plasma Cmax are estimated to be 0.23 (0.07) mcg/mL and 0.22 (0.07) mcg/mL in nAMD and in DME patients, respectively.

After repeated intravitreal administrations, mean plasma free faricimab trough concentrations are predicted to be 0.002-0.003 mcg/mL for Q8W dosing.

Although not directly measured in the vitreous, no accumulation of faricimab is expected in the vitreous and no accumulation has been observed in plasma when faricimab has been administered as repeat doses in the vitreous.

Metabolism/Elimination -                                                                                 Metabolism and elimination of faricimab has not been fully characterized.

Faricimab is expected to be catabolized in lysosomes to small peptides and amino acids, which may be excreted renally, in a similar manner to the elimination of endogenous IgG

. The estimated mean apparent systemic half-life of faricimab is 7.5 days.

Specific Populations-                                                                                                        The systemic pharmacokinetics of faricimab were not influenced by gender, race, or mild to severe renal impairment (i.e., estimated normalized creatinine clearance by Cockroft-Gault equation: 15 to 89 mL/min/1.73 m2).

The effect of severe renal impairment or any degree of hepatic impairment on the pharmacokinetics of VABYSMO is unknown. No special dosage modification is required for any of the populations that have been studied (e.g., elderly, gender, race).

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary -                                                                                  There are no adequate and well-controlled studies of VABYSMO administration in pregnant women.

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.

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.

3. Females and Males of Reproductive Potentia-                                       

l 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.

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

5. Geriatric Use-                                                                                                               In the four clinical studies, approximately 60% (1,149/1,929) 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.