Empaveli

Pegcetacoplan · Injection, Solution · Subcutaneous

Boxed warning. WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type B [see Warnings and Precautions (5.1) ] . Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated…

Uses

1 INDICATIONS AND USAGE EMPAVELI is a complement inhibitor indicated: for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH). ( 1.1 ) for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria and the loss of kidney function. ( 1.2 ) 1.1 Paroxysmal Nocturnal Hemoglobinuria EMPAVELI ® is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH). 1.2 C3 Glomerulopathy or Primary Immune-Complex Membranoproliferative Glomerulonephritis EMPAVELI ® is indicated for the treatment of adult and pediatric patients aged 12 years and older with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN), to reduce proteinuria and the loss of kidney function.

Dosage and administration

2.2 ) Recommended dosage is 1,080 mg administered subcutaneously twice weekly. C3G or Primary IC-MPGN ( 2.3 ) Recommended dosage for adults is 1,080 mg administered subcutaneously twice weekly. Recommended dosage for pediatric patients is dependent upon patient weight. See full prescribing information for the recommended dosage in patients with C3G or primary IC-MPGN. EMPAVELI can be administered via a commercially available pump or with EMPAVELI Injector. ( 2.4 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.2 , 2.3 , 2.4 ) 2.1 Recommended Vaccination and Prophylaxis Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis (serogroups A, C, W, Y and B), according to current ACIP recommendations at least 2 weeks prior to initiation of EMPAVELI therapy [see Warnings and Precautions (5.1) ] . If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines for Streptococcus pneumoniae and Neisseria meningitidis , according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. Healthcare professionals who prescribe EMPAVELI must enroll in the REMS for EMPAVELI [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage - PNH The recommended dose of EMPAVELI is 1,080 mg administered subcutaneously twice weekly [see Dosage and Administration (2.4) ]. Dosage for patients switching to EMPAVELI from C5 inhibitors To reduce the risk of hemolysis with abrupt treatment discontinuation: For patients switching from eculizumab, initiate EMPAVELI while continuing eculizumab at its current dose. After 4 weeks, discontinue eculizumab before continuing on monotherapy with EMPAVELI. For patients switching from ravulizumab, initiate EMPAVELI no more than 4 weeks after the last dose of ravulizumab. Dose Adjustment For lactate dehydrogenase (LDH) levels greater than 2 × the upper limit of normal (ULN), adjust the dosing regimen to 1,080 mg every three days. In the event of a dose increase, monitor LDH twice weekly for at least 4 weeks. Missed Dose Administer EMPAVELI as soon as possible after a missed dose. Resume the regular dosing schedule following administration of the missed dose. 2.3 Recommended Dosage - C3G or Primary IC-MPGN For adults (18 years and older) The recommended dose of EMPAVELI is 1,080 mg (20 mL) administered subcutaneously twice weekly [see Dosage and Administration (2.4) ] . For pediatric patients (12 years to less than 18 years of age) For pediatric patients 12 years of age and older, administer EMPAVELI dose and volume based upon body weight, according to the schedule in Table 1. Administer the recommended dose of EMPAVELI subcutaneously twice weekly [see Dosage and Administration (2.4) ] . Table 1: Dosing recommendation in C3G or primary IC-MPGN Patient Body Weight First dose (infusion volume) Second dose (infusion volume) Maintenance dose (infusion volume) 50 kg or higher 1,080 mg (20 mL) 1,080 mg (20 mL) 1,080 mg twice weekly (20 mL) 35 kg to less than 50 kg 648 mg (12 mL) 810 mg (15 mL) 810 mg twice weekly (15 mL) Less than 35 kg 540 mg (10 mL) 540 mg (10 mL) 648 mg twice weekly (12 mL) Missed Dose Administer EMPAVELI as soon as possible after a missed dose. Resume the regular dosing schedule following administration of the missed dose. 2.4 Administration EMPAVELI is for subcutaneous administration using: A commercially available infusion pump with a reservoir of at least 20 mL OR EMPAVELI Injector, a single-use, disposable on body injector EMPAVELI is intended for use under the guidance of a healthcare professional. Patients may self-administer or caregivers may administer EMPAVELI after proper training by a healthcare professional on how to prepare and administer EMPAVELI. Follow the steps below and use aseptic technique to prepare and administer EMPAVELI, either by an infusion pump or EMPAVELI Injector: Prior to use‚ allow EMPAVELI to reach room temperature 20°C to 25°C (68°F to 77°F) for approximately 30 minutes. Keep the vial in the carton until ready for use to protect from light. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. EMPAVELI is a clear, colorless to slightly yellowish solution. Do not use if the liquid looks cloudy, contains particles, or is dark yellow. Discard any unused portion of EMPAVELI. Preparation with Infusion Pump Refer to the EMPAVELI Instructions for Use and the infusion pump manufacturer's instructions for full preparation and administration information. Use a needleless transfer device (such as a vial adapter) or a transfer needle to fill the syringe. Rotate infusion sites (i.e., abdomen, thighs, hips, upper arms) from one infusion to the next. Do not infuse where the skin is tender, bruised, red, or hard. Avoid infusing into tattoos, scars, or stretch marks. If multi-infusion sets are needed, ensure the infusion sites are at least 3 inches apart. The typical infusion time is approximately 30 minutes (if using two infusion sites) or approximately 60 minutes (if using one infusion site). Preparation with EMPAVELI Injector Refer to the EMPAVELI Injector Instructions for Use, which comes with the device. Use a needleless transfer device (such as a vial adapter). EMPAVELI Injector is for abdominal subcutaneous use only. Rotate the site of each subcutaneous administration. Do not inject where the skin is tender, bruised, red, or hard. Avoid injecting into tattoos, scars, or stretch marks. Injection time is approximately 30 to 60 minutes.

Dosage forms and strengths

Injection: 1,080 mg/20 mL (54 mg/mL) clear, colorless to slightly yellowish solution in a single-dose vial. Injection: 1,080 mg/20 mL (54 mg/mL) in a single-dose vial. ( 3 )

Contraindications

4 CONTRAINDICATIONS EMPAVELI is contraindicated: in patients with hypersensitivity to pegcetacoplan or to any of the excipients [see Warnings and Precautions (5.3) ] . for initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type B [see Warnings and Precautions (5.1) ] . EMPAVELI is contraindicated: in patients with hypersensitivity to pegcetacoplan or any of the excipients. ( 4 ) for initiation in patients with unresolved serious infection caused by encapsulated bacteria. ( 4 )

Warnings and precautions

Serious infections caused by encapsulated bacteria. ( 5.1 ) Infusion-Related Reactions: Monitor patients for infusion-related reactions and institute appropriate medical management as needed. ( 5.3 ) Interference with Laboratory Tests: Use of silica reagents in coagulation panels may result in artificially prolonged activated partial thromboplastin time (aPTT). ( 5.5 ) 5.1 Serious Infections Caused by Encapsulated Bacteria EMPAVELI, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae , Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that, ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including EMPAVELI. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections. EMPAVELI is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ]. 5.2 EMPAVELI REMS EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria [see Warnings and Precautions (5.1) ] . Notable requirements of the EMPAVELI REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious infections caused by encapsulated bacteria. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for encapsulated bacteria and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of EMPAVELI. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and the patient is not up to date with vaccinations against encapsulated bacteria according to current ACIP recommendations at least two weeks prior to the first dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified. Patients must receive counseling from the prescriber about the need to receive vaccinations against encapsulated bacteria per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of serious infections. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 2 months following treatment discontinuation with EMPAVELI. Further information is available at www.empavelirems.com or 1-888-343-7073 5.3 Infusion-Related Reactions Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria, pyrexia) have occurred in patients treated with EMPAVELI, which may resolve after treatment with antihistamines. Cases of anaphylaxis leading to treatment discontinuation have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved. 5.4 Monitoring PNH Manifestations after Discontinuation of EMPAVELI After discontinuing treatment with EMPAVELI, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues EMPAVELI for at least 8 weeks to detect hemolysis and other reactions. If hemolysis, including elevated LDH, occurs after discontinuation of EMPAVELI, consider restarting treatment with EMPAVELI.

Side effects

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infections Caused by Encapsulated Bacteria [see Warnings and Precautions (5.1) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] The most common adverse reactions in patients with PNH (incidence ≥10%) were injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, pain in extremity, hypokalemia, fatigue, viral infection, cough, arthralgia, dizziness, headache, and rash. ( 6.1 ) The most common adverse reactions in patients with C3G or primary IC-MPGN (incidence ≥10%) were infusion site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. ( 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. Paroxysmal Nocturnal Hemoglobinuria Study in Complement-Inhibitor Experienced Adult Patients with PNH (Study APL2-302) The data described below reflect the exposure in 80 adult patients with PNH who received EMPAVELI (n=41) or eculizumab (n=39) at the recommended dosing regimens for 16 weeks. Serious adverse reactions were reported in 7 (17%) patients with PNH receiving EMPAVELI. The most common serious adverse reaction in patients treated with EMPAVELI was infections (5%). The most common adverse reactions (≥10%) with EMPAVELI were injection-site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, viral infection, and fatigue. Table 2 describes the adverse reactions that occurred in ≥5% of patients treated with EMPAVELI in Study APL2-302. Table 2: Adverse Reactions Reported in ≥5% of Patients Treated with EMPAVELI in Study APL2-302 Adverse Reaction EMPAVELI (N=41) n (%) Eculizumab (N=39) n (%) General disorders and administration site conditions Injection-site reaction Grouped terms Term includes injection-site erythema, injection-site reaction, injection-site swelling, injection-site induration, injection-site bruising, injection-site pain, injection-site pruritus, vaccination site reaction, administration site swelling, injection-site hemorrhage, injection -site edema, injection-site warmth, administration site pain, application site pain, injection-site mass, injection-site rash, vaccination site pain 16 (39) 2 (5) Fatigue 5 (12) 9 (23) Chest pain 3 (7) 1 (3) Infections and infestations Infections 12 (29) 10 (26) Respiratory tract infection 6 (15) 5 (13) Viral Infection 5 (12) 3 (8) Gastrointestinal disorders Diarrhea 9 (22) 1 (3) Abdominal pain 8 (20) 4 (10) Musculoskeletal disorders Back pain 3 (7) 4 (10) Nervous system disorders Headache 3 (7) 9 (23) Vascular disorders Systemic hypertension 3 (7) 1 (3) Clinically relevant adverse reactions in less than 5% of patients include: Intestinal ischemia Biliary sepsis Hypersensitivity pneumonitis After the randomized control period, 77 patients continued the study, and all were treated with EMPAVELI monotherapy at the recommended dosing regimen for up to 48 weeks. Serious adverse reactions were reported in 18 patients (23%). Additional adverse reactions reported in >5% of patients treated with EMPAVELI during the open-label part of the study compared to the randomized controlled part in Table 1 were cough (12%), arthralgia (8%), oropharyngeal pain (8%), pyrexia (8%), pain in extremity (7%), thrombocytopenia (7%), abdominal distension (5%), acute kidney injury (5%), anxiety (5%), and myalgia (5%). One patient (1%) died due to COVID-19 infection. Description of Select Adverse Reactions Injection-Site Reactions Injection/infusion-site reactions (e.g., erythema, swelling, induration, pruritus, and pain) have been reported during Study APL2-302. These reactions were mild or moderate in severity. Diarrhea Seventeen cases of diarrhea have been reported during the 48 weeks. Fifteen of the cases were mild and two were moderate. Study in Complement-Inhibitor Naïve Adult Patients with PNH (Study APL2-308) The data described below reflect the exposure in adult patients with PNH who received EMPAVELI (n=46) or the control arm (supportive care excluding complement inhibitors) (n=18) in Study APL2-308 [see Clinical Studies (14.1) ] . One patient (2%) who received EMPAVELI died due to septic shock. Serious adverse reactions were reported in 6 (13%) patients with PNH receiving EMPAVELI. The most common adverse reaction (≥10%) in patients treated with EMPAVELI were injection site reactions, infections, viral infection, pain in extremity, hypokalemia, arthralgia, dizziness, abdominal pain, rash, and headache. Table 3 describes the adverse reactions that occurred in ≥5% of patients treated with EMPAVELI in Study APL2‑308. Table 3: Adverse Reactions Reported in ≥5% of Patients Treated with EMPAVELI in Study APL2-308 Adverse Reaction EMPAVELI (N=46) n (%) Control Arm Control Arm = supportive care (excluding complement inhibitors) (N=18) n (%) Exposure Adjusted Rate (per 100 pt yrs) Exposure Adjusted Rate (per 100 pt yrs) EMPAVELI (N=46) group includes patients who received EMPAVELI at any point during the study, including patients randomized to EMPAVELI (N=35) and patients randomized to the control arm and crossed over to EMPAVELI treatment (N=11). General disorders and administration site conditions Injection-site reaction Grouped terms Term includes injection-site bruising, injection-site hemorrhage, injection-site swelling, application site reaction, infusion-site pruritus, injection-site erythema, injection-site rash, puncture site reaction.

Use in specific populations

8.1 Pregnancy Risk Summary There are insufficient data on EMPAVELI use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH in pregnancy (see Clinical Considerations ) . The use of EMPAVELI may be considered following an assessment of the risks and benefits. Treatment of pregnant cynomolgus monkeys with pegcetacoplan at a subcutaneous dose of 28 mg/kg/day (2.9 times human exposure based on AUC) from the gestation period through parturition resulted in a statistically significant increase in abortions or stillbirths compared to controls (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or fetal/neonatal risk PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery. Data Animal Data Animal reproduction studies with pegcetacoplan were conducted in cynomolgus monkeys. Pegcetacoplan treatment of pregnant cynomolgus monkeys at a subcutaneous dose of 28 mg/kg/day (2.9 times human exposure based on AUC) from the gestation period through parturition resulted in a statistically significant increase in abortions and stillbirths compared to controls. No increase in abortions or stillbirths occurred at a dose of 7 mg/kg/day (1.3 times human exposure based on AUC). No maternal toxicity or teratogenic effects were observed in offspring delivered at term. No developmental effects were observed in infants up to 6 months postpartum. Systemic exposure to pegcetacoplan of less than 1% of maternal levels was detected in fetuses from monkeys treated with 28 mg/kg/day from the period of organogenesis through the second trimester. 8.2 Lactation Risk Summary It is not known whether pegcetacoplan is secreted in human milk or whether there is potential for absorption and harm to the infant. There are no data on the effects of pegcetacoplan on milk production. Pegcetacoplan is present in milk of lactating monkeys (see Animal Data ) . Since many medicinal products are secreted into human milk, and because of the potential for serious adverse reaction in a breastfeeding child, breastfeeding should be discontinued during treatment and for 40 days after the last dose. Data Animal Data Pegcetacoplan was detectable in milk of lactating monkeys at less than 1% concentration of serum levels but was not detectable in the serum of nursing infants. 8.3 Females and Males of Reproductive Potential Contraception Females EMPAVELI may cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose. 8.4 Pediatric Use The safety and effectiveness of EMPAVELI for the treatment of C3G or primary IC-MPGN have been established in pediatric patients aged 12 years and older. Use of EMPAVELI for this indication is supported by evidence from an adequate and well controlled trial that enrolled 55 pediatric patients aged 12 years and older [see Adverse Reactions (6.1) , and Clinical Studies (14.2) ] . The safety and effectiveness of EMPAVELI in pediatric patients less than 12 years of age with C3G or primary IC-MPGN have not been established. Safety and effectiveness of EMPAVELI in pediatric patients with PNH have not been established. 8.5 Geriatric Use Clinical studies of EMPAVELI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients.

Pregnancy

Pediatric use

8.4 Pediatric Use The safety and effectiveness of EMPAVELI for the treatment of C3G or primary IC-MPGN have been established in pediatric patients aged 12 years and older. Use of EMPAVELI for this indication is supported by evidence from an adequate and well controlled trial that enrolled 55 pediatric patients aged 12 years and older [see Adverse Reactions (6.1) , and Clinical Studies (14.2) ] . The safety and effectiveness of EMPAVELI in pediatric patients less than 12 years of age with C3G or primary IC-MPGN have not been established. Safety and effectiveness of EMPAVELI in pediatric patients with PNH have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of EMPAVELI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients.

Description

11 DESCRIPTION EMPAVELI contains pegcetacoplan, a complement inhibitor. Pegcetacoplan is a symmetrical molecule comprised of two identical pentadecapeptides covalently bound to the ends of a linear 40-kiloDalton (kDa) 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. EMPAVELI injection is a sterile, clear, colorless to slightly yellowish aqueous solution for subcutaneous use and is supplied in a 20-mL single-dose vial. Each 1 mL of solution contains 54 mg of pegcetacoplan, 41 mg of sorbitol, 0.384 mg of glacial acetic acid, 0.490 mg of sodium acetate trihydrate, and Water for Injection USP. EMPAVELI may also contain sodium hydroxide and/or additional glacial acetic acid for adjustment to a target pH of 5. Chemical Structure

Mechanism of action

12.1 Mechanism of Action Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation. In PNH, extravascular hemolysis (EVH) is facilitated by C3b opsonization while intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC). Pegcetacoplan acts proximally in the complement cascade controlling both C3b-mediated EVH and terminal complement-mediated IVH. In C3G and primary IC-MPGN, complement dysregulation and overactivation causes deposition of C3 fragments in glomeruli, which contributes to the pathogenesis of C3G and is thought to contribute to the pathogenesis of primary IC-MPGN. Pegcetacoplan binds C3 and its activation fragment C3b, therefore inhibiting C3 activation, decreasing C3 glomerular fragment deposition, and decreasing C5 convertase activity and subsequent assembly of C5b-9.

How supplied

How Supplied EMPAVELI injection is a clear, colorless to slightly yellowish aqueous solution for subcutaneous infusion supplied as 1,080 mg/20 mL (54 mg/mL) solution in 20-mL single-dose vials. EMPAVELI is available in 20-mL single-dose vials individually packaged in cartons that are supplied in 8-count convenience cartons. NDC 73606-010-01. Storage and Handling Store vials of EMPAVELI refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not use beyond the expiration date stamped on the carton.

Storage

Storage and Handling Store vials of EMPAVELI refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not use beyond the expiration date stamped on the carton.

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Dosing For weight-based dosing, instruct caregivers and patients on the proper techniques for preparing, storing, measuring, and administering EMPAVELI via EMPAVELI Injector or commercially available infusion pump. Serious Infections Caused by Encapsulated Bacteria Advise patients of the risk of serious infection. Inform patients of the need to complete or update their vaccinations against encapsulated bacteria at least 2 weeks prior to receiving the first dose of EMPAVELI or receive antibacterial drug prophylaxis if EMPAVELI treatment must be initiated immediately and they have not been previously vaccinated. Inform the patient that they are required to be revaccinated according to current ACIP recommendations for encapsulated bacteria while on EMPAVELI therapy [see Warnings and Precautions (5.1) ] . Inform patients that vaccination may not prevent serious infection and strongly advise patients to seek immediate medical attention if these signs or symptoms occur. These signs and symptoms include the following: fever with or without shivers or the chills fever with chest pain and cough fever with breathlessness/fast breathing fever with high heart rate headache and a fever headache with a stiff neck or stiff back fever and a rash confusion headache with nausea or vomiting body aches with flu-like symptoms clammy skin eyes sensitive to light Inform patients that they will be given a Patient Safety Card for EMPAVELI that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient to seek immediate medical evaluation. EMPAVELI REMS EMPAVELI is available only through a restricted program called EMPAVELI REMS [see Warnings and Precautions (5.2) ] . Inform the patient of the following notable requirements: Patients must receive counseling about the risk of serious infections caused by encapsulated bacteria. Patients must receive written educational materials about this risk. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 2 months following treatment with EMPAVELI. Patients must be instructed to complete or update vaccinations against encapsulated bacteria per ACIP recommendations as directed by the prescriber prior to treatment with EMPAVELI. Patients must receive antibiotics as directed by the prescriber if they are not up to date with vaccinations against encapsulated bacteria and have to start EMPAVELI right away. Anaphylaxis and infusion-related reactions Advise patients of the risk of anaphylaxis and infusion-related reactions. Inform patients that anaphylaxis is life-threatening and strongly advise patients to seek immediate medical attention if these signs or symptoms occur. These signs and symptoms include the following: difficulty breathing including shortness of breath and wheezing swollen tongue or throat feeling faint rapid heart rate skin reactions, including hives and itching nausea or vomiting confusion and anxiety dizziness or fainting Discontinuation Inform patients with PNH that they may develop hemolysis due to PNH when EMPAVELI is discontinued and that they will be monitored by their healthcare professional for at least 8 weeks following discontinuation of EMPAVELI. Inform patients who discontinue EMPAVELI to keep the Patient Safety Card with them for 2 months after the last dose of EMPAVELI, because the increased risk of serious infection persists for several weeks following discontinuation of EMPAVELI.

Label text from the FDA structured product label by Apellis Pharmaceuticals, Inc. (revised Aug 21, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Pegcetacoplan in 1 product

Empaveli NDC products (1)

NDC	Strength & form	Labeler	Type
73606-010	Pegcetacoplan 1080 mg/20mL Injection, Solution	Apellis Pharmaceuticals, Inc.	NDA

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Empaveli is listed by 1 labeler in the FDA NDC directory, including Apellis Pharmaceuticals, Inc..