EMPAVELI was studied in
complement inhibitor–naïve
patients in the PRINCE trial1
The PRINCE trial was a Phase 3, randomized 2:1, open-label, 26-week trial that enrolled 53 patients with PNH on stable doses of medications and treatments, excluding complement inhibitors, which were sustained during the trial. One treatment group received EMPAVELI and the comparative control group did not.1
PRINCE trial particulars1
  • The trial consisted of a screening period of up to 4 weeks, followed by an RCP of 26 weeks
  • All subjects who completed Week 26 were eligible to roll over into a long-term extension trial
  • If, at any point during the study, any subject assigned to the control arm (excluding complement inhibitors) had Hb concentrations ≥2 g/dL below the baseline value or presented with a qualifying thromboembolic event secondary to PNH, they were offered early escape therapy with EMPAVELI
Peg is a real EMPAVELI patient.
Select inclusion criteria
Baseline characteristics
Adults with PNH, ≥18 years, not treated with C5 inhibitors for the previous 3 months1
Hb level below LLN at screening1
LDH level ≥1.5× ULN at screening1
Patient baseline demographics and characteristics in
PRINCE1
Parameter
Statistics
EMPAVELI
(n=35)
Soc
(n=18)
Age (years) Mean (SD) 42.2 (12.7) 49.1 (15.64)
Sex
Female n (%) 23 (65.7) 8 (4.4)
Race
Asian n (%) 23 (65.7) 16 (88.9)
American Indian or Alaska Native n (%) 9 (25.7) 2 (11.1)
Black or African American n (%) 2 (5.7) 0
Other n (%) 1 (2.9) 1 (1.9)
Ethnicity
Hispanic or Latino n (%) 12 (34.3) 2 (11.1)
Not Hispanic or Latino n (%) 23 (65.7) 16 (88.9)
Hemoglobin level (g/dL)
Mean (SD) 9.4 (1.4) 8.7 (0.8)
Absolute reticulocyte count (X 109/L)
Mean (SD) 230.2 (81.0) 180.3 (109.0)
LDH level (U/L)
Mean (SD) 2151.0 (909.4) 1946.0 (1003.7)
Number of transfusions in last 12 months prior to Day 28
Mean (SD) 3.9 (4.4) 5.1 (5.0)
<4 n (%) 21 (60.0) 8 (44.4)
≥4 n (%) 14 (40.0) 10 (55.6)
Patients included in PRINCE had varying transfusion history
(<4 or ≥4 transfusions in prior year)1
PRINCE trial design1
prince trial design image
A total of 53 patients were randomized (2:1 ratio) to receive either EMPAVELI or to remain on their current treatment (excluding complement inhibitors).1
New, concomitant use of these medications was prohibited unless patient was on a stable regimen for the time period indicated below prior to screening2:
  • Erythropoietin or immunosuppressants for at least 8 weeks
  • Systemic corticosteroids for at least 4 weeks
  • Vitamin K antagonists (eg, warfarin) with a stable INR for at least 4 weeks
  • Iron supplements, vitamin B12, or folic acid for at least 4 weeks
  • Low molecular weight heparin for at least 4 weeks
PRINCE trial endpoints
Coprimary endpoints1
  • Hb stabilization (avoidance of a >1 g/dL decrease in Hb levels in the absence of transfusions through Week 26)
  • Change from baseline in LDH levels at Week 26
Selected secondary endpoint1
  • Incidence and severity of adverse events (including study deaths) through Week 26
checklist image
Discover the PRINCE data
See results
Hb=hemoglobin; INR=international normalized ratio; LDH=lactate dehydrogenase; LLN=lower limit of normal; PNH=paroxysmal nocturnal hemoglobinuria; RCP=randomized control period; ULN=upper limit of normal.

References: 1. 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. 2. Data on file. Apellis Pharmaceuticals, Inc., Waltham, MA.

Indication and Important Safety Information

INDICATION

EMPAVELI® (pegcetacoplan) is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

IMPORTANT SAFETY INFORMATION

EMPAVELI® (pegcetacoplan) is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

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.