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EMPAVELI
safety profile
safety profile
PEGASUS: EMPAVELI safety profile at Week 161
Serious adverse reactions were reported in 17% of patients treated with EMPAVELI1
- The most common serious adverse reaction was infections (5%)1
The most common adverse reactions (≥10%) with EMPAVELI vs eculizumab, respectively, in the PEGASUS study1
-
Injection-site reactions: 39% vs 5%
- Injection-site reactions were mild or moderate in severity, with none leading to study discontinuation1
- Infections: 29% vs 26%
-
Diarrhea: 22% vs 3%
- All diarrhea cases were mild and did not lead to study discontinuation1
- Abdominal pain: 20% vs 10%
- Respiratory tract infection: 15% vs 13%
- Viral infection: 12% vs 8%
- Fatigue: 12% vs 23%
Clinically relevant adverse reactions in less than 5% of patients include1:
- Intestinal ischemia
- Biliary sepsis
- Hypersensitivity pneumonitis
Adverse reactions reported in ≥5% of patients treated with EMPAVELI1
| Adverse reactions |
EMPAVELI
(n=41)
n (%)
|
eculizumab
(n=39)
n (%)
|
|---|---|---|
|
General disorders and administration site conditions
|
||
| Injection site reaction* | 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) |
*The following terms were combined:
Abdominal pain
includes: abdominal pain upper, abdominal discomfort, abdominal pain, abdominal pain lower, abdominal tenderness, epigastric discomfort; Back pain
includes: back pain, sciatica; Chest pain
includes: chest discomfort, non-cardiac chest pain, musculoskeletal chest pain, chest pain; Fatigue
includes: asthenia, lethargy, fatigue; Infections
include: oral herpes, bacterial infection, fungal infection, gastrointestinal infection, gastrointestinal viral infection, influenza-like illness, nasopharyngitis, pulpitis dental, rhinitis, tonsillitis, tonsillitis bacterial, vulvovaginal mycotic infection, hordeolum, sepsis, furuncle, otitis externa, viral respiratory tract infection, gastroenteritis, upper respiratory tract infection, bronchitis, ear infection, respiratory tract infection, rhinovirus infection, sinusitis, urinary tract infection; Injection site reaction
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; Respiratory tract infection
includes: influenza-like illness, nasopharyngitis, rhinitis, tonsillitis, viral upper respiratory tract infection, upper respiratory tract infection, respiratory tract infection, sinusitis; Systemic hypertension
includes: hypertension; Viral infection
includes: oral herpes, gastrointestinal viral infection, viral upper respiratory tract infection, rhinovirus infection.1
NO NEW SAFETY SIGNALS IDENTIFIED THROUGH WEEK 482
- Most common AEs† reported in 48 weeks were injection site reactions (36%), hemolysis (24%), diarrhea (21%), nasopharyngitis (18%), headache (14%), fatigue (13%), cough (13%), and upper respiratory infection (11%)2
- One death reported due to COVID-19; unrelated to trial treatment2
- 12 of 80 (15%) patients discontinued due to TEAEs
- 5 patients discontinued due to hemolysis
†Most common AEs recorded during RCP + OLP follow-up periods.2
PRINCE: EMPAVELI safety profile at Week 263
Adverse events observed through Week 26 of the PRINCE trial3
| Adverse reactions |
Overall EMPAVELI‡
(n=46)
|
Control arm (excluding C5i)
(n=18)
|
|---|---|---|
|
Any AE, n (%)
|
33 (71.7) | 12 (66.7) |
| AEs related to EMPAVELI | 13 (28.3) | NA |
|
Serious AEs, n (%)
|
4 (8.7) | 3 (16.7) |
| Serious AEs related to EMPAVELI | 0 | NA |
|
AE by Severity, n (%)
|
||
| Mild or moderate | 29 (63.1) | 10 (55.6) |
| Severe | 4 (8.7) | 2 (11.1) |
|
Most Common TEAEs, n (%)
|
||
| Injection site reaction | 14 (30.4) | 0 |
| Hypokalemia | 6 (13.0) | 2 (11.1) |
| Dizziness | 5 (10.9) | 0 |
| Fever | 4 (8.7) | 0 |
TRIAL DEATHS AND SERIOUS AEs3
- No deaths or serious AEs deemed related to EMPAVELI occurred
- Two deaths unrelated to the trial drug occurred
- EMPAVELI group: 1 death due to bone marrow failure and septic shock
- Control arm group: 1 death due to severe febrile neutropenia
OTHER AEs3
- Most AEs in the EMPAVELI group were of mild (34.8%) or moderate severity (28.3%)
- Overall, there were no EMPAVELI-related AEs leading to drug or trial discontinuation
- No events of acute hemolysis were observed in either treatment group through Week 26
‡ Overall EMPAVELI includes the original EMPAVELI group (n=35) and the patients who received EMPAVELI treatment upon escape from the control arm group to the EMPAVELI group (n=11). Control arm excluded complement inhibitors eculizumab or ravulizumab.
REMS Program Information
VACCINATION REQUIREMENTS
The Risk Evaluation and Mitigation Strategy program for EMPAVELI1
Because of the risk of serious infections, EMPAVELI is available only through a restricted program under a REMS. Under the EMPAVELI REMS, prescribers must enroll in the program.
Prescribers must counsel patients about the risk of serious infection, provide patients with REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria.
Enrollment in the EMPAVELI REMS and additional information are available by telephone: 1‑888‑343-7073 or at www.empavelirems.com.
Prescribers must enroll in the REMS program before writing a prescription for EMPAVELI. Prescribers will only need to register once.
What to know before prescribing EMPAVELI to your patients1
Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B at least 2 weeks prior to initiation of EMPAVELI therapy according to current Advisory Committee on Immunization Practices (ACIP) guidelines.
Provide 2 weeks of antibacterial drug prophylaxis to patients if EMPAVELI must be initiated immediately and vaccines are administered less than 2 weeks before starting therapy with EMPAVELI.
Healthcare professionals who prescribe EMPAVELI must enroll in the REMS for EMPAVELI.
Indication and Important Safety Information
WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA 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.
- Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria.
- Vaccinate patients at least 2 weeks prior to administering the first dose of EMPAVELI unless the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection.
- 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.
CONTRAINDICATIONS
- Hypersensitivity to pegcetacoplan or to any of the excipients
- Not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying EMPAVELI treatment outweigh the risks of developing a bacterial infection with an encapsulated organism
- Unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae
WARNINGS AND PRECAUTIONS
Serious Infections Caused by Encapsulated Bacteria
The use of EMPAVELI may predispose individuals to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B (Hib). To reduce the risk of infection, all patients must be vaccinated against these bacteria according to the most current ACIP recommendations for patients with altered immunocompetence associated with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI.
For patients without known history of vaccination, administer required vaccines at least 2 weeks prior to receiving the first dose of EMPAVELI. If immediate therapy with EMPAVELI is indicated, administer required vaccine as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis.
Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of EMPAVELI in patients who are undergoing treatment for serious infections.
EMPAVELI REMS
Because of the risk of serious infections, EMPAVELI is available only through a restricted program under a REMS. Under the EMPAVELI REMS, prescribers must enroll in the program and must counsel patients about the risk of serious infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria. Enrollment and additional information are available by telephone: 1-888-343-7073 or at www.empavelirems.com.
Infusion-Related Reactions
Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria) have occurred in patients treated with EMPAVELI. One patient (less than 1% in clinical studies) experienced a serious allergic reaction which resolved after treatment with antihistamines. 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.
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.
Interference with Laboratory Tests
There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥10% of patients) with EMPAVELI vs. eculizumab were injection-site reactions (39% v. 5%), infections (29% v. 26%), diarrhea (22% v. 3%), abdominal pain (20% v. 10%), respiratory tract infection (15% v. 13%), viral infection (12% v. 8%), and fatigue (12% v. 23%).
USE IN SPECIFIC POPULATIONS
Females of Reproductive Potential
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.
Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.
AE=adverse event; OLP=open-label period; RCP=randomized control period; REMS=Risk Evaluation and Mitigation Strategy; TEAE=treatment-emergent adverse event.
References: 1. EMPAVELI [prescribing information]. Waltham, MA: Apellis Pharmaceuticals, Inc.; 2021. 2. Data on file. Apellis Pharmaceuticals, Inc., Waltham, MA. 3. Wong RS, Navarro JR, Comia NS, et al. Efficacy and safety of pegcetacoplan treatment in complement-inhibitor naïve patients with paroxysmal nocturnal hemoglobinuria: results from the phase 3 PRINCE study. Abstract presented at: 63rd ASH Annual Meeting; December 11-14, 2021; Atlanta, GA.
Indication and Important Safety Information
WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA 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.
- Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria.
- Vaccinate patients at least 2 weeks prior to administering the first dose of EMPAVELI unless the risks of delaying therapy with EMPAVELI outweigh the risk of developing a serious infection.
- 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.
CONTRAINDICATIONS
- Hypersensitivity to pegcetacoplan or to any of the excipients
- Not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying EMPAVELI treatment outweigh the risks of developing a bacterial infection with an encapsulated organism
- Unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae
WARNINGS AND PRECAUTIONS
Serious Infections Caused by Encapsulated Bacteria
The use of EMPAVELI may predispose individuals to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B (Hib). To reduce the risk of infection, all patients must be vaccinated against these bacteria according to the most current ACIP recommendations for patients with altered immunocompetence associated with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI.
For patients without known history of vaccination, administer required vaccines at least 2 weeks prior to receiving the first dose of EMPAVELI. If immediate therapy with EMPAVELI is indicated, administer required vaccine as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis.
Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of EMPAVELI in patients who are undergoing treatment for serious infections.
EMPAVELI REMS
Because of the risk of serious infections, EMPAVELI is available only through a restricted program under a REMS. Under the EMPAVELI REMS, prescribers must enroll in the program and must counsel patients about the risk of serious infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria. Enrollment and additional information are available by telephone: 1-888-343-7073 or at www.empavelirems.com.
Infusion-Related Reactions
Systemic hypersensitivity reactions (e.g., facial swelling, rash, urticaria) have occurred in patients treated with EMPAVELI. One patient (less than 1% in clinical studies) experienced a serious allergic reaction which resolved after treatment with antihistamines. 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.
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.
Interference with Laboratory Tests
There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥10% of patients) with EMPAVELI vs. eculizumab were injection-site reactions (39% v. 5%), infections (29% v. 26%), diarrhea (22% v. 3%), abdominal pain (20% v. 10%), respiratory tract infection (15% v. 13%), viral infection (12% v. 8%), and fatigue (12% v. 23%).
USE IN SPECIFIC POPULATIONS
Females of Reproductive Potential
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.
Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.
