Pegcetacoplan

FDA Drug Information • Also known as: Empaveli, Syfovre

Brand Names: Empaveli, Syfovre
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION SYFOVRE contains pegcetacoplan, a complement inhibitor. Pegcetacoplan is a symmetrical molecule composed of two identical pentadecapeptides covalently bound to the ends of a linear 40 kiloDalton (kDa) polyethylene glycol (PEG) molecule. The peptide portions of pegcetacoplan contain 1-methyl-L-tryptophan (Trp(Me)) in position 4 and amino (ethoxyethoxy) acetic acid (AEEA) in position 14. The molecular weight of pegcetacoplan is approximately 43.5 kDa. The molecular formula is C 1970 H 3848 N 50 O 947 S 4 . The structure of pegcetacoplan is shown below. SYFOVRE (pegcetacoplan injection) is a sterile, clear, colorless to light yellow aqueous solution in a single-dose vial for intravitreal use. Each vial allows for the delivery of 0.1 mL of solution containing 15 mg pegcetacoplan, trehalose dihydrate (5.95 mg), glacial acetic acid (0.0895 mg), sodium acetate trihydrate (0.0353 mg), and Water for Injection. SYFOVRE may also contain sodium hydroxide and/or additional glacial acetic acid for adjustment to a target pH of 5.0. SYFOVRE does not contain an anti-microbial preservative. Chemical Formula

What Is Pegcetacoplan Used For?

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 )

Dosage and Administration

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...

Side Effects (Adverse Reactions)

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.

Contraindications

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) ] .

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of SYFOVRE administration in pregnant women to inform a drug-associated risk. The use of SYFOVRE may be considered following an assessment of the risks and benefits. Systemic exposure of SYFOVRE following ocular administration is low [see Clinical Pharmacology (12.3) ] . Subcutaneous administration of pegcetacoplan to pregnant monkeys from the mid gestation period through birth resulted in increased incidences of abortions and stillbirths at systemic exposures 1040-fold higher than that observed in humans at the maximum recommended human ophthalmic dose (MRHOD) of SYFOVRE (based on the area under the curve (AUC) systemically measured levels). No adverse maternal or fetal effects were observed in monkeys at systemic exposures approximately 470-fold higher than that observed in humans at the MRHOD (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In embryofetal development studies, subcutaneous administration of pegcetacoplan to pregnant cynomolgus monkeys from the mid gestation period through birth produced increased incidences of abortions and stillbirths at doses of 28 mg/kg/day [approximately 1040-fold higher than the MRHOD based on exposure (AUC)]. Pegcetacoplan was not maternally toxic and did not produce adverse embryofetal effects in the monkey at subcutaneous doses of 7 mg/kg/day. (approximately 470-fold higher than the MRHOD). No developmental effects were observed in infants up to 6 months postpartum. Minimal systemic exposure to pegcetacoplan (less than 1%, not pharmacologically significant) was detected in fetuses from monkeys treated subcutaneously with 28 mg/kg/day from the period of organogenesis through the second trimester.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied SYFOVRE (pegcetacoplan injection) is supplied as a clear, colorless to light yellow aqueous solution. Each glass vial contains an overfill amount to allow for administration of a single 0.1 mL dose of solution containing 15 mg of SYFOVRE. SYFOVRE packaging options are included in Table 3. Table 3: Packaging Options NDC Number Carton Type Carton Contents 73606-020-02 Vial Kit with Injection Components 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 One prescribing information 73606-020-01 Vial Only One SYFOVRE vial One prescribing information 16.2 Storage and Handling Refrigerate SYFOVRE between 2°C to 8°C (36°F to 46°F). Store the vial in the original carton to protect from light. Do not use beyond the expiration date on the carton. Do not shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.