Long-term integrated analysis design1
/ About EMPAVELI / Long-term efficacy and safety evaluated
in integrated analysis1
IMPORTANT SAFETY INFORMATION
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. 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 risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
- Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS.
CONTRAINDICATIONS
- Hypersensitivity to pegcetacoplan or to any of the excipients
- For initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B
WARNINGS AND PRECAUTIONS
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 initiation 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. 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.
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. Notable requirements of the EMPAVELI REMS include the following:
Under the EMPAVELI REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card both during treatment, as well as for 2 months following last dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified.
Further information is available at www.empavelirems.com or 1-888-343-7073.
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
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.
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.
INDICATION
EMPAVELI® (pegcetacoplan) is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).
Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide.
STUDY DESIGN1
This integrated analysis of data from the EMPAVELI Phase 3 trials (PEGASUS, PRINCE) and subsequent open-label extension evaluated long-term efficacy and safety. Overall, 114 of the 133 patients in the Phase 3 trials enrolled in the extension study (PEGASUS [n=64], PRINCE [n=50]).
Long-term data presented reflect the subset of patients who received 1080 mg of EMPAVELI by subcutaneous infusion twice weekly or every 3 days for up to 3 years (2.5 years, PRINCE; 3 years, PEGASUS).
Original inclusion criteria were baseline Hb <10.5 g/dL despite ≥3 months of stable eculizumab dosing (PEGASUS) or naïve to complement inhibitors with Hb <LLN (13.6 g/dL for males, 12.0 g/dL for females) (PRINCE) at screening.
Limitations:
- Data from this post hoc, integrated analysis are descriptive in nature, collected for observation only
- The analysis included a mixed patient population—C5i-experienced (PEGASUS) and complement inhibitor-naïve (PRINCE). Findings may not represent all people with PNH
- Baseline for those not originally assigned EMPAVELI in the trials was defined by when they started receiving EMPAVELI to evaluate the long-term effectiveness and safety of treatment with EMPAVELI
Long-term Hb and LDH efficacy data2,*,†
Long-term sustained Hb data2
Observed median values in Hb (g/dL) up to 3 years2
Patients who had a transfusion were not included in the Hb analysis for 60 days after the transfusion.1
Normal range of Hb: 12 to 16 g/dL for females, 13.6 to 18 g/dL for males.2
Long-term sustained LDH data2
Observed median values in LDH (U/L) up to 3 years2
LDH normalization is defined as 113 to 226 U/L.2
*Baseline: baseline laboratory value of patients upon initiation of EMPAVELI, regardless of when in the trials this occurred.1,2
†Data reflect the subset of patients who received 1080 mg of EMPAVELI by subcutaneous infusion twice weekly or every 3 days.1
Long-term safety data
Long-term integrated analysis safety up to 3 years
- The most common AEs (≥10%) were infections and infestations (75.8%), injection site reactions (36.4%), abdominal pain (18.2%), fatigue (18.2%), headache (16.7%), and cough (12.1%)—consistent with those reported in the original trials2
- Two serious AEs deemed related to EMPAVELI occurred (1 case of biliary sepsis in PEGASUS and 1 case of sepsis in PRINCE)2
- No new or unexpected safety findings were identified2
AE=adverse event; Hb=hemoglobin; LDH=lactate dehydrogenase; LLN=lower limit of normal; PNH=paroxysmal nocturnal hemoglobinuria; ULN=upper limit of normal.
References: 1. de Castro CM, Mulherin B, Patriquin CJ, et al. Efficacy and safety is maintained in adult patients with paroxysmal nocturnal hemoglobinuria receiving pegcetacoplan for up to 3 years. 65th ASH Annual Meeting and Exposition. 2023. 2. Data on file. Apellis Pharmaceuticals, Inc., Waltham, MA.
