VABYSMO Dailymed

Recent Major Changes Section

Indications and Usage, Macular Edema Following Retinal Vein Occlusion (RVO) (1.3)	10/2023
Dosage and Administration, General Dosing Information (2.1)	7/2024
Dosage and Administration, Macular Edema Following Retinal Vein Occlusion (2.4)	10/2023
Dosage and Administration, Preparation for Administration - Prefilled Syringe (2.5)	7/2024
Dosage and Administration, Injection Procedure (2.7)	7/2024
Warnings and Precautions, Retinal Vasculitis and/or Retinal Vascular Occlusion (5.4)	10/2023

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)

1.1Neovascular (wet) Age-Related Macular Degeneration (nAMD)

1.2Diabetic Macular Edema (DME)

1.3 Macular Edema Following Retinal Vein Occlusion (RVO)

2 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) for 6 months. (2.4)

2.1General 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)]

2.2Neovascular (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.

2.3Diabetic 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) for 6 months.

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.
	Do not use if the injection filter needle is missing.
	Do not remove the finger grip from the syringe.
	Do not use if the syringe cap is detached from the Luer lock.
	Do not use if particulates, cloudiness, or discoloration are visible. VABYSMO is a clear to opalescent and colorless to brownish-yellow liquid solution.
Prefilled Syringe Description
	Figure A
Note: the dose must be set to the 0.05 mL dose mark.
Use aseptic technique to carry out the following preparation steps:
Open Tray and Remove Syringe Cap
1	Peel the lid off the syringe tray and aseptically remove the prefilled syringe.
2	Hold the syringe by the white collar; snap off the syringe cap (see Figure B ).
	Do not twist off the cap.
	Figure B
Attach Injection Filter Needle
3	Aseptically remove the provided injection filter needle from its packaging.
4	Aseptically and firmly attach the injection filter needle onto the syringe Luer lock (see Figure C ).
	Figure C
5	Carefully remove the needle cap by pulling it straight off.
Dislodge Air Bubbles
6	Hold the syringe with the injection filter needle pointing up. Check the syringe for air bubbles.
7	If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure D ).
	Figure D
Expel Air and Adjust the Dose
8	Hold the syringe at eye level and slowly push the plunger rod until the lower edge of the rubber stopper's dome is aligned with the 0.05 mL dose mark (see Figure E ). This will expel the air and the excess solution and set the dose to 0.05 mL.
	Ensure that the injection is given immediately after preparation of the dose.
	Figure E

2.6Preparation for Administration - Vial

Note that a 30-gauge injection needle is recommended to avoid increased injection forces that could be experienced with smaller diameter needles.

One sterile injection needle 30-gauge × ½ inch (not included)

Alcohol swab (not included).

 

Before you start
	Read all the instructions carefully before using VABYSMO.
	The VABYSMO kit includes a glass vial and transfer filter needle. The glass vial is for a single dose only. The filter needle is for treatment of a single eye.
	VABYSMO should be stored refrigerated at temperatures between 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake.
	Allow VABYSMO to reach room temperature, 20°C to 25°C (68°F to 77°F) before proceeding with the administration. Keep the vial in the original carton to protect from light.
	The VABYSMO vial may be kept at room temperature for up to 24 hours.
	The VABYSMO vial should be inspected visually for particulate matter and discoloration prior to administration. VABYSMO is a clear to opalescent and colorless to brownish-yellow liquid solution. Do not use if particulates, cloudiness, or discoloration are visible. Do not use if the packaging, vial and/or transfer filter needle are expired, damaged, or have been tampered with (see Figure F ).
	Figure F
Use aseptic technique to carry out the preparation of the intravitreal injection.
1	Gather the following supplies: One VABYSMO vial (included) One sterile 5-micron blunt transfer filter needle 18-gauge × 1½ inch (included) One sterile 1 mL Luer lock syringe with a 0.05 mL dose mark (not included)
2	To ensure all liquid settles at the bottom of the vial, place the vial upright on a flat surface (for about 1 minute) after removal from packaging (see Figure G ). Gently tap the vial with your finger (see Figure H ), as liquid may stick to the top of the vial.
	Figure G	Figure H
3	Remove the flip-off cap from the vial (see Figure I ) and wipe the vial septum with an alcohol swab (see Figure J ).
	Figure I	Figure J
4	Aseptically and firmly attach the included 18-gauge × 1½ inch transfer filter needle onto a 1 mL Luer lock syringe (see Figure K ).
	Figure K
5	Using aseptic technique, push the transfer filter needle into the center of the vial septum (see Figure L ), push it all the way in, then tilt the vial slightly so that the needle touches the bottom edge of the vial (see Figure M ).
	Figure L	Figure M
6	Hold the vial slightly inclined and slowly withdraw all the liquid from the vial (see Figure N ). Keep the bevel of the transfer filter needle submerged in the liquid, to avoid introduction of air.
	Figure N
7	Ensure that the plunger rod is drawn sufficiently back when emptying the vial, in order to completely empty the transfer filter needle (see Figure N ).
8	Disconnect the transfer filter needle from the syringe and dispose of it in accordance with local regulations.
	          Do not use the transfer filter needle for the intravitreal injection.
9	Aseptically and firmly attach a 30-gauge × ½ inch injection needle onto the Luer lock syringe (see Figure O ).
	Figure O
10	Carefully remove the plastic needle shield from the needle by pulling it straight off.
11	To check for air bubbles, hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top (see Figure P ).
	Figure P
12	Carefully expel the air from the syringe and needle, and slowly depress the plunger to align the rubber stopper tip to the 0.05 mL dose mark. The syringe is ready for the injection (see Figure Q ). Ensure that the injection is given immediately after preparation of the dose.
	Figure Q

2.7 Injection Procedure

The intravitreal injection procedure must be carried out under aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent), and the availability of sterile paracentesis equipment (if required). Adequate anesthesia and a broad-spectrum microbicide should be administered prior to the injection.

Inject slowly until the rubber stopper reaches the end of the syringe to deliver the volume of 0.05 mL.

Note for the prefilled syringe: Do not recap or detach the injection filter needle from the syringe.

Any unused drug product or waste material should be disposed of in accordance with local regulations.

Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available. Following intravitreal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., vision loss, eye pain, redness of the eye, photophobia, blurring of vision) without delay [see Patient Counseling Information (17)].

Each syringe should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new syringe should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before VABYSMO is administered to the other eye.

• 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)

5.1Endophthalmitis 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)].

5.2Increase 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)].

5.3Thromboembolic 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)].

5.4Retinal 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.

6 Adverse Reactions

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)
	AMDN=664	DMEN=1,262	RVON=641	AMDN=662	DMEN=625	RVON=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 tearAMD only	3%			1%
Intraocular pressure increased	3%	4%	1%	2%	3%	3%
Eye pain	3%	3%	< 1%	3%	3%	< 1%
Intraocular inflammationIncluding 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.

8 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.

8.3Females 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.

8.4Pediatric 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.