Izervay

General Dosing Information

IZERVAY must be administered by a qualified physician.

Recommended Dosage

The recommended dose for IZERVAY is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly (approximately every 28 ± 7 days).

Preparation for Administration

Important information you should know before you begin:

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Read all the instructions carefully before using IZERVAY.

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The IZERVAY kit includes a glass vial, filter needle, and an empty syringe. The glass vial, filter needle, and empty syringe are for single use only.

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Store IZERVAY in the refrigerator at temperatures between 2ºC to 8ºC (36ºF to 46ºF). Do not freeze. Do not shake.

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Prior to use, allow IZERVAY to reach room temperature, 20⁰C to 25⁰C (68⁰F to 77⁰F). The IZERVAY vial may be kept at room temperature for up to 24 hours. Keep the vial in the original carton to protect from light.

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

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Each vial should only be used for the treatment of a single eye.

Step 1: Gather Supplies   Gather the following supplies (see Figure A): a. One IZERVAY vial (included) b. One sterile 5-micron filter needle 18-gauge x 1½ inch (included) c. One sterile 1 mL Luer lock syringe with a 0.1 mL dose mark (included) d. One sterile injection needle 30‑gauge x ½ inch (not included)   NOTE: a 30-gauge injection needle is recommended to avoid increased injection forces that could be experienced with smaller diameter needles. e. Alcohol swab (not included)

Figure A

Step 2: Inspect Vial   Inspect the liquid in the vial. It should be a clear to slightly opalescent, colorless to slightly yellow liquid solution (see Figure B).   Do not use if particulates, cloudiness, or discoloration are visible.     Do not use if the packaging, vial, filter needle, injection needle, and/or empty syringe are expired, damaged, or have been tampered with.

Figure B

Step 3: Orient Vial   Place the vial upright on a flat surface for about 1 minute after removal from packaging to make sure all liquid settles at the bottom of the vial (see Figure C).   Gently tap the vial with your finger to remove any liquid that may stick to the top of the vial (see Figure D).

Figure C ______________________________________ Figure D

Step 4: Clean Vial   Remove the flip-off cap from the vial (see Figure E).   Gently wipe the vial septum with an alcohol swab (see Figure F).

Figure E                                                                                              Figure F

Step 5: Attach Filter Needle   Using aseptic technique, firmly attach the included 18-gauge x 1½ inch filter needle onto the 1 mL Luer lock syringe and twist clockwise to secure (see Figure G).

Figure G

Step 6: Insert Filter Needle into Vial   Using aseptic technique, push the filter needle all the way into the center of the vial septum (see Figure H).   Tilt the vial slightly so that the needle touches the bottom edge of the vial (see Figure I).   Rotate the filter needle so that the bevel is submerged into the liquid to avoid introduction of air.

Figure H                                                                                                       Figure I

Step 7: Withdraw Liquid   Slowly withdraw all the liquid from the vial (see Figure J).   Draw the plunger rod back far enough to completely empty the filter needle.

Figure J

Step 8: Disconnect Filter Needle   Disconnect the filter needle from the syringe and dispose of it in accordance with local regulations (see Figure K).   Do not use the filter needle for the intravitreal injection.

Figure K

Step 9: Attach Injection Needle   Using aseptic technique, firmly attach the 30-gauge x ½ inch injection needle onto the Luer lock syringe. (see Figure L). Carefully remove the plastic needle shield from the needle by pulling it straight off (see Figure M).

Figure L ________________________________________ Figure M

Step 10: Check Syringe   Check for air bubbles by holding 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 N).

Figure N

Step 11: Prepare Appropriate Dose   Slowly depress the plunger to: • Expel the air from the syringe • Align the rubber stopper tip to the 0.1 mL dose mark. The syringe is now ready for the injection (see Figure O).   Make sure to give the injection immediately after preparing the dose.

Figure O

Injection Procedure

Only 0.1 mL (2 mg) should be administered to deliver a single dose. Any excess volume should be disposed.

Prior to the intravitreal injection, patients should be monitored for elevated intraocular pressure (IOP) using tonometry [see Warnings and Precautions (5.3)]. If necessary, ocular hypotensive medication can be given to lower the IOP.

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

Inject slowly until the rubber stopper reaches the end of the syringe to deliver the volume of 0.1 mL. Confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel.

Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure (IOP). Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry.

Following intravitreal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay [see Patient Counseling Information (17)].

Each vial and syringe should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial and syringe should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter needle, and injection needle should be changed before IZERVAY is administered to the other eye. Repeat the same procedure steps as above.

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

Pregnancy

Risk Summary

There are no adequate and well-controlled studies of IZERVAY administration in pregnant women. The use of IZERVAY may be considered following an assessment of the risks and benefits.

Administration of avacincaptad pegol to pregnant rats and rabbits throughout the period of organogenesis resulted in no evidence of adverse effects to the fetus or pregnant female at intravenous (IV) doses 5.5 times and 3.4 times the human exposure, respectively, based on Area Under the Curve (AUC), following a single 2 mg intravitreal (IVT) dose (see Data).

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15%-20%, respectively.

Data

Animal Data

An embryo fetal developmental toxicity study was conducted with pregnant rats. Pregnant rats received daily IV injections of avacincaptad pegol from day 6 to day 17 of gestation at 0.1, 0.4, 1.2 mg/kg/day. No maternal or embryofetal adverse effects were observed at any dose evaluated. An increase in the incidence of a non-adverse skeletal variation, described as short thoracolumbar (ossification site without distal cartilage) supernumerary ribs, was observed at all doses evaluated. The clinical relevance of this finding is unknown. Plasma exposures at the high dose were 5.5 times the human AUC of 999 ng•day/mL (23976 ng•hr/mL) following a single 2 mg IVT dose.

An embryo fetal developmental toxicity study was conducted with pregnant rabbits. Pregnant rabbits received daily IV injections of avacincaptad pegol from day 7 to day 19 of gestation at 0.12, 0.4, 1.2 mg/kg/day. No maternal or embryofetal adverse effects were observed at any dose evaluated. Plasma exposure in pregnant rabbits at the highest dose of 1.2 mg/kg/day was 3.4 times the human AUC of 999 ng•day/mL (23976 ng•hr/mL) following a single 2 mg IVT dose.

Lactation

Risk Summary

There is no information regarding the presence of avacincaptad pegol in human milk, the effects of the drug on the breastfed infant, or the effects of avacincaptad pegol 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 IZERVAY, and any potential adverse effects on the breastfed infant from IZERVAY.

Pediatric Use

Safety and effectiveness of IZERVAY in pediatric patients have not been established.

Geriatric Use

Of the total number of patients who received IZERVAY in the two clinical trials, 90% (263/292) were ≥65 years and 61% (178/292) were ≥75 years of age. No significant differences in efficacy or safety of avacincaptad pegol were seen with increasing age in these studies. No dose adjustment is required in patients 65 years and above.

Endophthalmitis and Retinal Detachments

Intravitreal injections may be associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1)]. Proper aseptic injection techniques must always be used when administering IZERVAY in order to minimize the risk of endophthalmitis [see Dosage and Administration (2.4)]. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management [see Patient Counseling Information (17)].

Neovascular AMD

In the GATHER1 and GATHER2 clinical trials, use of IZERVAY was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (7% when administered monthly and 4% in the sham group) by Month 12. Over 24 months, the rate of neovascular (wet) AMD or choroidal neovascularization in the GATHER2 trial was 12% in the IZERVAY group and 9% in the sham group. Patients receiving IZERVAY should be monitored for signs of neovascular AMD.

Increase in Intraocular Pressure

Transient increases in intraocular pressure (IOP) have been observed after an intravitreal injection, including with IZERVAY [see Adverse Reactions (6.1)]. Perfusion of the optic nerve head should be monitored following the injection and managed as needed [see Dosage and Administration (2.4)].