FDA Approves Empaveli (pegcetacoplan) for Adults with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in targeted C3 therapies, today announced that the U.S. Food and Drug Administration (FDA) has approved Empaveli™ (pegcetacoplan), the first and only targeted C3 therapy for treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Empaveli is approved for use in adults with PNH who are treatment naïve as well as patients switching from the C5 inhibitors Soliris® (eculizumab) and Ultomiris® (ravulizumab).

“Empaveli has the potential to improve the lives of patients with PNH by increasing hemoglobin and reducing blood transfusion requirements,” said Olga Frankfurt, M.D., PEGASUS study investigator and associate professor in the department of medicine, division of hematology and oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Through my work as an investigator on the PEGASUS study, I was excited to see Empaveli providing broad control of PNH."

“As the first, FDA-approved targeted C3 therapy, Empaveli has the potential to redefine treatment for adults with PNH, including patients switching from any C5 inhibitor and treatment-naïve patients. Thank you to the clinical trial participants, PNH community, investigators, healthcare professionals, SFJ Pharmaceuticals, and more who helped contribute to this significant milestone,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer, Apellis. “This approval represents a major scientific advancement as Empaveli ushers in the first new class of complement medicine in almost 15 years. We look forward to exploring the full potential of targeting C3 and continue to advance registrational programs of this therapy across multiple complement-driven diseases with high unmet need.”

The approval of Empaveli is based on results from the head-to-head Phase 3 PEGASUS study, which were recently published in the New England Journal of Medicine. In the PEGASUS study, Empaveli met the primary endpoint, demonstrating superiority to Soliris for the change from baseline in hemoglobin level at Week 16 with an adjusted mean increase of 3.84 g/dL of hemoglobin (p<0.0001). Additionally, Empaveli met non-inferiority compared to Soliris on the endpoint of transfusion avoidance. Eighty five percent of Empaveli-treated patients were transfusion free over 16 weeks versus 15% of Soliris-treated patients.

“We are pleased to hear of the FDA’s decision to approve Empaveli, which is an important milestone for patients,” said Janice Frey-Angel, chief executive officer and executive director, Aplastic Anemia and MDS International Foundation (AAMDSIF). “Many PNH patients are seeking choices in their treatment, so the approval brings new promise for the PNH community.”

The prescribing information for Empaveli contains a boxed warning. Empaveli may increase the risk of meningococcal and other serious infections caused by encapsulated bacteria that may become rapidly life threatening or fatal if not recognized and treated early. A Risk Evaluation and Mitigation Strategy (REMS) has been approved by the FDA for Empaveli. Prescribers must counsel patients about the risk of serious infection, provide patients with the REMS educational materials, and ensure patients are vaccinated against encapsulated bacteria.

The most common serious adverse reaction in patients treated with Empaveli was infections (5%). The most common adverse reactions (≥10%) with Empaveli were injection site reactions (39%), infections (29%), diarrhea (22%), abdominal pain (20%), respiratory tract infection (15%), viral infection (12%), and fatigue (12%). No cases of meningitis and no deaths were reported in patients treated with Empaveli.

PNH is a rare, chronic, life-threatening blood disorder caused by an acquired mutation, which leads to uncontrolled complement activation and the destruction of red blood cells through intravascular and extravascular hemolysis. According to a retrospective and a cross-sectional study of patients treated with C5 inhibitors, at least 72% had persistently low hemoglobin1,2 and at least 36% required one or more transfusions a year.

Apellis is committed to helping patients with treatment access and support. ApellisAssist™ is a program designed to provide comprehensive product support to Empaveli patients throughout their treatment journey. This program provides services and product resources including insurance support, education, training, as well as financial assistance for eligible patients. Patients and healthcare providers can contact 1-866-692-7527 for more information.

A Marketing Authorization Application for pegcetacoplan for the treatment of PNH is under review by the European Medicines Agency with the potential for a European Commission decision in the second half of 2021.

About the PEGASUS Study

The PEGASUS study (APL2-302; NCT03500549) is a multi-center, randomized, head-to-head Phase 3 study in 80 adults with paroxysmal nocturnal hemoglobinuria (PNH). The primary objective of this study was to establish the efficacy and safety of Empaveli™ (pegcetacoplan) compared to Soliris® (eculizumab). Participants must have been on Soliris (stable for at least three months) with a hemoglobin level of <10.5 g/dL at the screening visit. During the four-week run-in, patients were dosed with 1080 mg of Empaveli twice weekly (n=41) in addition to their current dose of Soliris. During the 16-week randomized, controlled period, patients were randomized to receive either 1080 mg of Empaveli twice weekly or their current dose of Soliris (n=39). All participants completing the randomized controlled period (n=77) opted to enter the open-label Empaveli treatment period.

The study was conducted in collaboration with SFJ Pharmaceuticals, who supported the development of Empaveli in PNH. SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world’s top pharmaceutical and biotechnology companies.

About Empaveli™ (pegcetacoplan)

Empaveli™ (pegcetacoplan) is the first and only approved therapy targeting C3, the central protein in the complement cascade. Empaveli acts proximally in the complement cascade controlling both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis. Empaveli is approved in the United States for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

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.

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. 

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.

About the Apellis and Sobi Collaboration

Apellis and Sobi entered a collaboration to develop and commercialize systemic pegcetacoplan in October 2020. The companies have global co-development rights for systemic pegcetacoplan. Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and retains worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA). Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan.

About Apellis 

Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology.