Apellis Pharmaceuticals, Inc. announced that results from the long-term extension study of EMPAVELI® (pegcetacoplan) in adults with paroxysmal nocturnal hemoglobinuria will be presented at the American Society of Hematology (ASH) Annual Meeting being held Dec. 10-13 in New Orleans, Louisiana. The data show that EMPAVELI, the first and only targeted C3 therapy, demonstrated robust and sustained improvements in key markers of disease across a broad population of PNH patients for up to two years.

The new results reinforce the positive efficacy and safety of EMPAVELI in both treatment-naïve patients and patients who had previously been treated with eculizumab, a C5 inhibitor, across all five prior PNH clinical studies. After being treated with EMPAVELI for up to two years, mean hemoglobin was sustained at near-normal levels at 11.6 g/dl, 83% of patients were transfusion free, and 73% of patients had normalized levels of lactate dehydrogenase (LDH). Long-term safety data were consistent with previous clinical study results, with no thrombotic events or meningitis infections reported.

The most common adverse events (AEs) were hemolysis (17%) and injection site reactions. The APL2-307 study was a nonrandomized, open-label, multicenter Phase 3 extension study of 137 adults with paroxysmal nocturnal hemoglobinuria (PNH) who completed previous EMPAVELI®/Aspaveli® (pegcetacoplan) Phase 1 (PHAROAH, PADDOCK), Phase 2 (PALOMINO), and Phase 3 (PEGASUS, PRINCE) clinical trials. Patients in these studies were either anemic despite eculizumab treatment or were naïve to complement inhibitors.

During the 48-week trial period, patients continued to receive 1080 mg of EMPAVELI twice weekly or once every three days (PEGASUS, PRINCE) or switched to 1080 mg of EMPAVELI twice weekly (PHAROAH, PADDOCK, PALOMINO). The primary objective was to establish the long-term efficacy and safety of EMPAVELI. U.S. Important Safety Information for EMPAVELI BOXED 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.

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%).