Pegcetacoplan

12.1 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

1 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 )

2 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

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Ocular and periocular infections [see Contraindications (4.1) ] Active intraocular inflammation [see Contraindications (4.2) ] Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ] Retinal Vasculitis and/or Retinal Vascular Occlusion [see Warnings and Precautions (5.2) ] Neovascular AMD [see Warnings and Precautions (5.3) ] Intraocular inflammation [see Warnings and Precautions (5.4) ] Increased intraocular pressure [see Warnings and Precautions (5.5) ] Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apellis Pharmaceuticals, Inc. at 1-833-866-3346 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 the clinical trials of another drug and may not reflect the rates observed in practice. A total of 839 patients with GA in two Phase 3 studies (OAKS and DERBY) were treated with intravitreal SYFOVRE, 15 mg (0.1 mL of 150 mg/mL solution). Four hundred nineteen (419) of these patients were treated in the affected eye monthly and 420 were treated in the affected eye every other month. Four hundred seventeen (417) patients were assigned to sham. The most common adverse reactions (≥5%) reported in patients receiving SYFOVRE were ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage. Table 1: Adverse Reactions in Study Eye Reported in ≥2% of Patients Treated with SYFOVRE Through Month 24 in Studies OAKS and DERBY Adverse Reactions PM (N = 419) % PEOM (N = 420) % Sham Pooled (N = 417) % PM: SYFOVRE monthly; PEOM: SYFOVRE every other month Ocular discomfort The following reported terms were combined: Ocular discomfort included: eye pain, eye irritation, foreign body sensation in eyes, ocular discomfort, abnormal sensation in eye Neovascular age-related macular degeneration included: exudative age-related macular degeneration, choroidal neovascularization Punctate keratitis included: punctate keratitis, keratitis Intraocular inflammation included: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, anterior chamber flare 13 10 11 Neovascular age-related macular degeneration 12 7 3 Vitreous floaters 10 7 1 Conjunctival hemorrhage 8 8 4 Vitreous detachment 4 6 3 Retinal hemorrhage 4 5 3 Punctate keratitis 5 3 <1 Posterior capsule opacification 4 4 3 Intraocular inflammation 4 2 <1 Intraocular pressure increased 2 3 <1 Endophthalmitis, retinal detachment, hyphema and retinal tears were reported in less than 1% of patients. Optic ischemic neuropathy was reported in 1.7% of patients treated monthly, 0.2% of patients treated every other month and 0.0% of patients assigned to sham. Deaths were reported in 6.7% of patients treated monthly, 3.6% of patients treated every other month and 3.8% of patients assigned to sham. The rates and causes of death were consistent with the elderly study population. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of SYFOVRE. 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. Systemic reactions: anaphylaxis, rash, and urticaria.