Izervay Drug Information
Generic name: AVACINCAPTAD PEGOL
Uses of Izervay
IZERVAY ® is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Dosage & Administration of Izervay
General Dosing Information IZERVAY must be administered by a qualified physician.
Recommended Dosage
The recommended dosage 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: • Read all the instructions carefully before using IZERVAY. • 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. • Store IZERVAY in the refrigerator at temperatures between 2ºC to 8ºC (36ºF to 46ºF). Do not freeze.
Do not shake. • 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. • Use aseptic technique to carry out the preparation of the intravitreal injection. • Each vial should only be used for the treatment of a single eye.
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.
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. 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.
| 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 |
Side Effects of Izervay
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 the clinical trials of another drug and may not reflect the rates observed in practice. The safety of avacincaptad pegol was evaluated in 733 patients with AMD in two sham-controlled studies (GATHER1 and GATHER2). Three hundred thirty-two patients were assigned to sham.
Adverse reactions reported in ≥2% of patients who received treatment with IZERVAY for up to 12 months pooled across the GATHER1 and GATHER2 studies are listed below in Table 1. Table 2: Common Ocular Adverse Reactions (≥ 2%) and greater than Sham in Study Eye up to 24 months Photopsia, optic ischemic neuropathy, vitreous hemorrhage, vitreal cells, vitritis, and endophthalmitis were each reported in ≤ 1% of patients treated with IZERVAY for up to 24 months across the GATHER1 and GATHER2 studies.
| 1 Blurred vision includes visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently. | ||
| Adverse Drug Reactions | IZERVAY N=292 | Sham N=332 |
| Conjunctival hemorrhage | 13% | 9% |
| Increased IOP | 9% | 1% |
| Blurred vision 1 | 8% | 5% |
| Choroidal neovascularization | 7% | 4% |
| Eye pain | 4% | 3% |
| Vitreous floaters | 2% | <1% |
| Blepharitis | 2% | <1% |
| 1 Blurred vision includes visual impairment, vision blurred, visual acuity reduces, visual acuity reduced transiently and blindness transient. | ||
| 2 Punctate keratitis includes punctate keratitis and keratitis. | ||
| Adverse Drug Reactions | IZERVAY (N=225) | Sham (N=222) |
| Conjunctival hemorrhage | 17% | 9% |
| Blurred vision 1 | 14% | 5% |
| Increased IOP | 13% | 1% |
| Choroidal neovascularization | 12% | 9% |
| Punctate keratitis 2 | 10% | 8% |
| Eye pain | 7% | 4% |
| Retinal hemorrhage | 4% | 3% |
| Vitreous floaters | 4% | <1% |
| Ocular hypertension | 4% | 0 |
| Blepharitis | 3% | <1% |
| Corneal abrasion | 2% | <1% |
Warnings & Cautions for Izervay
Endophthalmitis and Retinal Detachments
Intravitreal injections may be associated with endophthalmitis and retinal detachments. Proper aseptic injection techniques must always be used when administering IZERVAY in order to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management.
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. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.
Pregnancy Safety for Izervay
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. 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.
Pediatric Use of Izervay
Pediatric Use Safety and effectiveness of IZERVAY in pediatric patients have not been established.
Contraindications for Izervay
Ocular or Periocular Infections IZERVAY is contraindicated in patients with ocular or periocular infections.
Active Intraocular Inflammation IZERVAY is contraindicated in patients with active intraocular inflammation.
Clinical Studies of Izervay
The safety and efficacy of IZERVAY were demonstrated in two randomized, multi-center, double-masked, sham-controlled, 18- and 24-month studies (GATHER1-NCT02686658 and GATHER2-NCT04435366, respectively) in patients with GA due to AMD. Patient ages ranged from 51 to 97 years with a mean of 77 years. In total, 292 patients were treated with avacincaptad pegol 2 mg, and 332 patients received sham.
In GATHER1, patients were treated with either IZERVAY or sham monthly for 18 months. In the primary analysis for GATHER1, the mean rate of GA growth (slope) from baseline to Month 12, measured by Fundus Autofluorescence (FAF), was evaluated at 3 time points: baseline, Month 6, and Month 12. Over a 12-month period, there was a statistically significant reduction of the rate of GA growth (0.10 mm/year; p<0.01 with square root transformed data) in patients treated with IZERVAY compared to sham.
The observed results are shown in Table 3 and Figure 1 below. In the 24-month GATHER2 study, patients were treated with IZERVAY or sham monthly for the first 12 months. Patients receiving monthly IZERVAY were re-randomized at Month 12 to receive either IZERVAY monthly (EM) or every other month (EOM).
Patients treated with sham in the first 12 months continued monthly sham treatment. At any time during the GATHER2 study, patients that developed choroidal neovascularization were concomitantly treated with anti-VEGF therapy. In the treatment arm that included patients who received IZERVAY EM treatment for one year and EOM treatment for the second year, the annualized rate of GA growth was 2.10 mm 2 /year.
In both studies, treatment effects in all pre-specified subgroups (e.g., age, gender, baseline GA disc area) were consistent with the results in the overall population.
| a = non-transformed GA growth slope analysis | ||||||
| b = % difference is calculated by 100*(difference)/(least squares mean from Sham) | ||||||
| c = IZERVAY EM (IZERVAY monthly in both year 1 and year 2) MMRM= Mixed Models for Repeated Measures | ||||||
| Efficacy Endpoint (MMRM Analysis) | Month 12 | Month 24 | ||||
| GATHER1 | GATHER2 | GATHER2 | ||||
| IZERVAY N=67 | Sham N=110 | IZERVAY N=225 | Sham N=222 | IZERVAY c N=96 | Sham N=203 | |
| GA Rate of Growth (mm 2 /year) (observed) a | 1.22 | 1.89 | 1.75 | 2.12 | 2.23 | 2.59 |
| Difference (95% CI) (mm 2 /year) Difference % b p value | 0.67 (0.21-1.13) 35% <0.01 | 0.38 (0.12-0.63) 18% <0.01 | 0.36 (0.07 – 0.66) 14% 0.0165 | |||
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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