VABYSMO™ (faricimab-svoa)

VABYSMO™ (faricimab-svoa) injection, for intravitreal use

VABYSMO™

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 glass vial for intravitreal administration. Each 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.

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)

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

DOSAGE AND ADMINISTRATION

For intravitreal injection. VABYSMO must be administered by a qualified physician. Each vial should only be used for the treatment of a single eye.

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.

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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 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.

Preparation for Administration

  1. 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 single use only.

VABYSMO should be stored refrigerated at temperatures between 2ºC to 8ºC (36ºF to 46ºF).

  • 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. The VABYSMO vial may be kept at room temperature for up to 24 hours.  Keep the vial in the original carton to protect from light.

VABYSMO 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

Use aseptic technique to carry out the preparation of the intravitreal injection.

VABYSMO™ a
  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)

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

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

Alcohol swab (not included).

  1. 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 B). Gently tap the vial with your finger (see Figure C), as liquid may stick to the top of the vial.
VABYSMO™ b

Figure B

VABYSMO™2 c

Figure C

  1. Remove the flip-off cap from the vial (see Figure D) and wipe the vial septum with an alcohol swab (see Figure E).
VABYSMO™ d

                                                                                Figure D

VABYSMO™ e

Figure E

  1. Aseptically and firmly attach the included 18-gauge × 1½ inch transfer filter needle onto a 1 mL Luer lock syringe (see Figure F).
VABYSMO™ f

Figure F

  1. Using aseptic technique, push the transfer filter needle into the center of the vial septum (see Figure G), push it all the way in, then tilt the vial slightly so that the needle touches the bottom edge of the vial (see Figure H).
VABYSMO™ g

Figure G

VABYSMO™ h

Figure H

  1. Hold the vial slightly inclined and slowly withdraw all the liquid from the vial (see Figure I). Keep the bevel of the transfer filter needle submerged in the liquid, to avoid introduction of air.
VABYSMO™ i

Figure I

  1. Ensure that the plunger rod is drawn sufficiently back when emptying the vial, in order to completely empty the transfer filter needle (see Figure I).
  1. 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.

  1. Aseptically and firmly attach a 30-gauge × ½ inch injection needle onto the Luer lock syringe (see Figure J).
VABYSMO™ j

Figure J

  1. Carefully remove the plastic needle shield from the needle by pulling it straight off.
  1. 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 K)
VABYSMO™ k

Figure K

  1. 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 L). Ensure that the injection is given immediately after preparation of the dose.
VABYSMO™ l

Figure L

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. Confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel.

Any unused medicinal 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. 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.

CONTRAINDICATIONS

Ocular or Periocular Infections: VABYSMO is contraindicated in patients with ocular or periocular infections.

Active Intraocular Inflammation: VABYSMO is contraindicated in patients with active intraocular inflammation.

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: Intravitreal injections have been associated with endophthalmitis and retinal detachments. Proper aseptic injection techniques must always be used when administering VABYSMO. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management

Increase in Intraocular Pressure: Transient increases in intraocular pressure (IOP) have been seen within 60 minutes of intravitreal injection, including with VABYSMO. IOP and the perfusion of the optic nerve head should be monitored and managed appropriately.

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).

ADVERSE REACTIONS

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

To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

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

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Lactation: 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.

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

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.

How Supplied

VABYSMO (faricimab-svoa) injection is supplied as a clear to opalescent, colorless to brownish-yellow 120 mg/mL solution in a single-dose glass vial. Each glass vial contains an overfill amount to allow for administration of a single 0.05 mL dose of solution containing 6 mg of VABYSMO.  Each VABYSMO carton (NDC 50242-096-01) contains one glass vial and one sterile 5-micron blunt transfer filter needle (18-gauge × 1½ inch, 1.2 mm × 40 mm).

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 vial in the original carton to protect from light.

Prior to use, the unopened 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.

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