20 ML pegcetacoplan 54 MG/ML Injection

INDICATIONS AND USAGE SYFOVRE is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). ( 1 )

DOSAGE AND ADMINISTRATION The recommended dose for SYFOVRE is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days. ( 2.2 ) 2.1 General Dosing Information SYFOVRE must be administered by a qualified physician. 2.2 Recommended Dosage The recommended dose for SYFOVRE is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days. 2.3 Preparation for Administration Store SYFOVRE in the refrigerator between 2°C to 8°C (36°F to 46°F); Keep the vial in the original carton to protect from light. SYFOVRE is available packaged as follows: Vial Only Vial Kit with Injection Components (filter needle, syringe, injection needle) Remove the carton from the refrigerator. Keep the vial in the original carton at room temperature 20°C to 25°C (68°F to 77°F), for at least 15 minutes prior to injection, but no longer than 8 hours. Fill the syringe immediately prior to the injection. Do not shake the vial. The vial is for use in a single eye. Inspect the solution. It is a clear, colorless to light yellow aqueous solution. Do not use if: particulates, cloudiness, or discoloration are visible, the vial shows signs of damage or tampering, the expiration date has passed the packaging or components show signs of damage or tampering STEP 1 Gather the supplies needed: One SYFOVRE vial One sterile 5-micron filter needle One sterile 1-mL Luer-lock syringe with a 0.1 mL dose mark One sterile ½ inch: 29-gauge (extra) thin-wall injection needle with Luer-lock hub (included with vial kit) or a 27-gauge needle with Luer-lock hub (not included) Note: Increased injection forces and/or increased injection time could be experienced if a smaller diameter injection needle is used (e.g., 30-gauge) Alcohol swab ( not included ) Use aseptic technique to carry out the following preparation steps: STEP 2 Remove the flip-off cap from the vial (see Figure 1a ) and clean the vial septum with an alcohol swab and wait for the alcohol to dry out (see Figure 1b ). Figure 1a: Figure 1b: STEP 3 Attach the 5-micron filter needle onto a 1-mL Luer-lock syringe (see Figure 2 ) by twisting it onto the Luer-lock syringe tip. Figure 2: STEP 4 Push the filter needle into the center of the vial septum until the needle is submerged in the drug product to prevent withdrawal of air (see Figure 3a ). To withdraw the entire contents of the vial into the syringe, hold the vial at a slightly inclined position. Withdraw the drug product slowly to prevent air bubbles. Continue to tilt the vial during withdrawal keeping the bevel of the filter needle submerged in the liquid until all of the fluid is withdrawn from the vial (see Figure 3b ). *Do not tap the syringe to remove air bubbles. While maintaining the filter needle within the vial, invert the syringe and move the plunger down and up until bubbles move to the top (see Figure 3c ). Figure 3a: Figure 3b: Figure 3c: STEP 5 Using aseptic technique, disconnect the filter needle from the syringe and dispose of it. Do not use the filter needle for injection. STEP 6 Aseptically and firmly attach the injection needle onto the 1-mL Luer-lock syringe (see Figure 4 ). Figure 4: STEP 7 Check for air bubbles by holding the syringe with the needle pointing up. * Do not tap the syringe to remove air bubbles. If there are any air bubbles, remove the needle cap and with the needle end facing up gently advance the plunger to the 0.1 mL dose mark (see Figure 5 ). Only 0.1 mL (15 mg of SYFOVRE) should be administered to deliver a single dose. Any excess volume should be disposed. The syringe is ready for injection. Figure 5: Figure Figure Figure Figure Figure 1a Figure 1b Figure 2 Figure 3a Figure 3b Figure 3c Figure 4 Figure 5 2.4 Injection Procedure Only 0.1 mL (15 mg of SYFOVRE) should be administered to deliver a single dose. Any excess volume should be disposed. Ensure that the injection is given immediately after the preparation of the dose. Prior to the intravitreal injection, patients should be monitored for elevated intraocular pressure (IOP) using tonometry [see Warnings and Precautions (5.4) ] . If necessary, ocular hypotensive medication can be given to lower the IOP. The intravitreal injection procedure should 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). Adequate anesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface should be administered prior to the injection. Inject slowly until the rubber stopper reaches the end of the syringe to deliver the volume of 0.1 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 elevations in IOP. Additional evaluation may include checking for perfusion of the optic nerve head and 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 should only be used for the treatment of a single eye. If the fellow eye requires treatment, a new sterile, vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before SYFOVRE administration. Repeat same procedure steps as above. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

WARNINGS AND PRECAUTIONS Endophthalmitis and Retinal Detachments ( 5.1 ) Retinal Vasculitis and/or Retinal Vascular Occlusion ( 5.2 ) Neovascular AMD ( 5.3 ) Intraocular inflammation ( 5.4 ) Increased Intraocular Pressure ( 5.5 ) 5.1 Endophthalmitis and Retinal Detachments Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1) ] . Proper aseptic injection technique must always be used when administering SYFOVRE 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 and should be managed appropriately. 5.2 Retinal 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 SYFOVRE [see Adverse Reactions (6.2) ] . Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay. 5.3 Neovascular AMD In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration. 5.4 Intraocular Inflammation In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves patients may resume treatment with SYFOVRE. 5.5 Increased Intraocular Pressure Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed [see Dosage and Administration (2.4) ] .

CONTRAINDICATIONS Ocular or Periocular Infections ( 4.1 ) Active Intraocular Inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections SYFOVRE is contraindicated in patients with ocular or periocular infections [see Warnings and Precautions (5.1) ] . 4.2 Active Intraocular Inflammation SYFOVRE is contraindicated in patients with active intraocular inflammation. 4.3 Hypersensitivity SYFOVRE is contraindicated in patients with hypersensitivity to pegcetacoplan or to any of the excipients in SYFOVRE. Systemic hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria) have occurred in patients treated with SYFOVRE [see Adverse Reactions (6.2) ] .

Mechanism of Action Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation