BRIEF SUMMARY

PEGCETACOPLAN- (May 2021)

Indn-   to treat adult patientswith paroxysmal  nocturnal hemoglobinuria    

Comp-    • Injection: 1,080 mg/20 mL (54 mg/mL) in a single-dose vial.                              • Recommended dosage is 1,080 mg by subcutaneous infusion twice weekly via a commercially available pump.  

ADR-  Most common adverse reactions in patients with PNHwere injection-site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, viral infection, and fatigue.

CI-   : • Patients with hypersensitivity to pegcetacoplan or any of the excipients.

 • Patients who are not currently vaccinated against certain encapsulated bacteria unless the risks of delaying  treatment outweigh the risks of developing a serious bacterial infection.

WARNINGS-

 Use caution when administering EMPAVELI to patients with:                                                • Serious infections caused by encapsulated bacteria.                                                        • Infusion-Related Reactions: Monitor patients for infusion-related reactions and institute appropriate medical management as needed. 

Pat inform-

Serious Infections Caused by Encapsulated Bacteria -Advise patients of the risk of serious infection. Inform patients that they are required to receive vaccinations against encapsulated bacteria at least 2 weeks prior to receiving the first dose  if they have not been previously vaccinated.

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 20

Name of the Drug-    EMPAVELLI

Active Ingredient -   Pegcetacoplan

Pharmacological Classification-   To treat adult patientswith paroxysmal

                                                          nocturnal hemoglobinuria                                                                                                                                                                                        Date of Approval-          5/14/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                                 EMPAVELI safely and effectively.                                                                                    See full prescribing information for EMPAVELI. EMPAVELI™ (pegcetacoplan) injection, for subcutaneous use

Initial U.S. Approval: 20XX

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA See full prescribing information for complete boxed warning.

Meningococcal infections may occur in patients treated with EMPAVELI and may become rapidly life-threatening or fatal if not recognized and treated early.

Use of EMPAVELI may predispose individuals to serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae,

Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B. (5.1).

• Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria

 • Vaccinate patients against encapsulated bacteria as recommended at least 2 weeks prior to administering the first dose of EMPAVELI unless the risks of delaying EMPAVELI therapy outweigh the risks of developing a serious infection. See Warnings and Precautions  for additional guidance on managing the risk of serious infections.

• Vaccination reduces, but does not eliminate, the risk of serious infections. Monitor patients for early signs of serious infections and evaluate immediately if infection is suspected.

 EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the EMPAVELI REMS, prescribers must enroll in the program.

INDICATIONS AND USAGE

 EMPAVELI is a complement inhibitor indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH). 

 ADVERSE REACTIONS- 

 Most common adverse reactions in patients with PNH (incidence =10%) were injection-site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, viral infection, and fatigue.

CONTRAINDICATIONS

 EMPAVELI is contraindicated in: • Patients with hypersensitivity to pegcetacoplan or any of the excipients.

 • Patients who are not currently vaccinated against certain encapsulated bacteria unless the risks of delaying EMPAVELI treatment outweigh the risks of developing a serious bacterial infection with an encapsulated organism.

 • Patients with unresolved serious infection caused by encapsulated bacteria. 

WARNINGS AND PRECAUTIONS

 Use caution when administering EMPAVELI to patients with:                                                • Serious infections caused by encapsulated bacteria.                                                        • Infusion-Related Reactions: Monitor patients for infusion-related reactions and institute appropriate medical management as needed.                                                                      • Interference with Laboratory Tests: Use of silica reagents in coagulation panels may result in artificially prolonged activated partial thromboplastin time (aPTT). 

INDICATIONS AND USAGE

 EMPAVELI is a complement inhibitor indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH). 

• Recommended dosage is 1,080 mg by subcutaneous infusion twice weekly via a commercially available pump.                                                                                              • See Full Prescribing Information for instructions on preparation and administration. 

 DOSAGE FORMS AND STRENGTHS-

 • Injection: 1,080 mg/20 mL (54 mg/mL) in a single-dose vial. 

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Serious Infections Caused by Encapsulated Bacteria -Advise patients of the risk of serious infection. Inform patients that they are required to receive vaccinations against encapsulated bacteria at least 2 weeks prior to receiving the first dose of EMPAVELI if they have not been previously vaccinated.

They are required to be revaccinated according to current medical guidelines for encapsulated bacteria while on EMPAVELI therapy.

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 and a rash • shortness of breath

• extreme pain or discomfor

• headache with nausea or vomiting

• high heart rate • headache and a fever

• headache with a stiff neck or stiff back

• confusion • muscle 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.

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. Reference ID: 4796130

Manufactured For: Apellis Pharmaceuticals, Inc. 100 Fifth Avenue Waltham, MA 02451 For patent information: www.apellis.com/productpatent Copyright © 20XX Apellis Pharmaceuticals, Inc. All rights reserved. EMPAVELI is a trademark of Apellis Pharmaceuticals, Inc. EMP-PI-XXMay2021-0.0 Reference ID: 479613

 CLINICAL PHARMACOLOGY

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.

2. Pharmacodynamics -                                                                                                 The mean C3 concentration increased from 0.94 g/L at baseline to 3.83 g/L at Week 16 in patients with PNH administered multiple doses of pegcetacoplan. The baseline percentage of PNH Type II + III RBCs was 66.8%, which increased to 93.9% at Week 16.

The mean percentage of PNH Type II + III RBCs with C3 deposition was 17.7% at baseline and decreased to 0.20% at Week 16.

Cardiac Electrophysiology -At the recommended dose of EMPAVELI, no large mean increases in QTc interval (i.e., greater than 20 msec) were observed.

3. Pharmacokinetics-                                                                                                  Steady-state serum pegcetacoplan concentrations were achieved approximately 4 to 6 weeks following the first dose and mean (%CV) steady-state trough serum concentrations ranged between 655 (18.6%) to 706 (15.1%) mcg/mL in patients with PNH treated for 16 weeks.

Exposure of pegcetacoplan increases proportionally over a dosage range from 45 to 1,440 mg (0.04 to 1.33 times the approved recommended dose)

Absorption -                                                                                                                      The median Tmax of pegcetacoplan is between 108 and 144 hours (4.5 to 6.0 days).

Distribution-                                                                                                                   The mean (%CV) volume of distribution of pegcetacoplan is approximately 3.9 L (35%) in patients with PNH.

Elimination-                                                                                                                    The estimated mean (CV%) of clearance (CL) is 0.37 L/day (28%) and median effective half-life of elimination (t1/2) is 8.0 days in patients with PNH.

Metabolism-                                                                                                             Pegcetacoplan is expected to be metabolized into small peptides and amino acids by catabolic pathways

Specific Populations-                                                                                                 There were no clinically significant differences on the pharmacokinetics of pegcetacoplan based on age (19 to 81 years old), sex, race (Asian vs. non-Asian), renal impairment, and hepatic function as evaluated by total bilirubin (0.3-4.3 mg/dL), albumin (3.6-4.9 g/dL), aspartate aminotransferase (13-116 IU/L), or alanine aminotransferase (9-61 IU/L).

USE IN SPECIFIC POPULATIONS

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.

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.

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.

3. Females and Males of Reproductive Potential-                                                  Contraception- Females EMPAVELI may cause embryo-fetal harm when administered to pregnant women 

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.

4. Pediatric Use-                                                                                                                Safety and effectiveness have not been established.

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.