Apellis and Sobi Report Empaveli™ (pegcetacoplan) Demonstrated Sustained Normalization of Clinical Measures in a Broad PNH Patient Population
- Improvements demonstrated in treatment-naïve patients and patients with baseline hemoglobin levels greater than or equal to 10.0 g/dL
- Data were presented at the American Society of Hematology (ASH) Annual Meeting
WALTHAM, Mass. and STOCKHOLM, Sweden, Dec. 13, 2021 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals Inc, (Nasdaq: APLS) and Swedish Orphan Biovitrum AB (publ) (Sobi™) (STO:SOBI) announced today new data demonstrating that Empaveli™/Aspaveli® (pegcetacoplan) provides consistent, sustained normalization of clinical measures across patients with paroxysmal nocturnal hemoglobinuria (PNH) who are treatment-naïve and patients with baseline hemoglobin levels greater than or equal to 10.0 g/dL. The data were presented at the American Society of Hematology Annual Meeting (ASH) taking place December 11 - 14, 2021.
Sustained Normalization and Superior Improvements of Clinical Measures in Treatment-Naïve Patients
New data from the Phase 3 PRINCE study in treatment-naïve patients with PNH showed that treatment with EMPAVELI resulted in sustained and superior improvements in the co-primary endpoints of hemoglobin stabilization through Week 26 and reduction in lactate dehydrogenase (LDH) compared to standard of care, which did not include complement inhibitors, at Week 26.
Improvements were seen as early as two weeks after starting treatment with EMPAVELI and patients showed sustained normalization across key markers of disease through Week 26:
- 46% of EMPAVELI patients achieved hemoglobin normalization in the absence of transfusions vs. 0% for standard of care (p<0.0010), reaching a mean hemoglobin level of 12.8 g/dL from a mean baseline of 9.4 g/dL
- Mean LDH levels rapidly fell from 9.5x the upper limit of normal (ULN) to below 1.5x the ULN by Week 2, normalized by Week 4, and were maintained through Week 26 with EMPAVELI
- 91% of EMPAVELI patients achieved transfusion avoidance vs. 6% for standard of care (p<0.0001), demonstrating superiority
The safety profile of EMPAVELI was consistent with previous studies. At Week 26, 9% of patients in the EMPAVELI group experienced a serious adverse event (SAE) compared to 17% on standard of care. No cases of thrombosis or meningococcal infection were reported in either group. The most common adverse events reported during the study in the EMPAVELI and standard of care groups, respectively, were injection site reaction (30% vs. 0%), hypokalemia (13% vs.11%), dizziness (11% vs. 0%), and fever (9% vs. 0%).
“The data presented at ASH add to a robust body of evidence that underscores the consistent efficacy and safety of EMPAVELI across a broad range of adults with PNH,” said Federico Grossi, M.D., Ph.D., chief medical officer of Apellis. “EMPAVELI has the potential to elevate the standard of care for adults with PNH regardless of prior treatment or baseline hemoglobin levels.”
Clinically Meaningful Improvements in Patients with Near-Normal Baseline Hemoglobin Levels
A new post hoc analysis across studies from the EMPAVELI PNH clinical development program showed that EMPAVELI-treated patients with baseline hemoglobin levels greater than or equal to 10.0 g/dL demonstrated clinically meaningful improvements across key markers of disease. The analysis included data from patients who were treatment-naïve and patients that remained anemic despite stable treatment with eculizumab, a C5 inhibitor.
Detailed data showed:
- EMPAVELI increased mean hemoglobin levels to 13.9 g/dL, 12.1 g/dL, and 12.7 g/dL from a mean baseline of 11.3 g/dL, 10.2 g/dL, and 10.4 g/dL in the PRINCE, PEGASUS, and PADDOCK studies, respectively
- EMPAVELI demonstrated mean improvements from baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score of 9.9 points, 13.3 points, and 6.6 points in the PRINCE, PEGASUS, and PADDOCK studies. A three-point improvement is generally considered to be clinically meaningful
“The presented data reinforce the efficacy and safety profile of pegcetacoplan in PNH,” said Ravi Rao, head of research and development and chief medical officer at Sobi. “We are committed to improve care, and to make a difference in the lives of people with this rare blood disease.”
About the PRINCE Study
The PRINCE study (NCT04085601) was a randomized, multi-center, open-label, controlled Phase 3 study in 53 treatment-naïve adults with paroxysmal nocturnal hemoglobinuria (PNH). The primary objective of this study was to establish the efficacy and safety of EMPAVELI™ (pegcetacoplan) in patients who have not received treatment with any complement inhibitor within three months prior to screening. During the 26-week randomized, controlled period, patients received either 1080 mg of EMPAVELI twice weekly or standard of care therapy, which did not include complement inhibitors. Patients in the standard of care group had the option to escape to the EMPAVELI group if their hemoglobin decreased by 2 g/dL or more from their baseline value.
About the PEGASUS Study
The PEGASUS study (NCT03500549) was 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 compared to eculizumab. Participants must have been on eculizumab (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 eculizumab. During the 16-week randomized, controlled period, patients were randomized to receive either 1080 mg of EMPAVELI twice weekly or their current dose of eculizumab (n=39). All participants completing the randomized controlled period (n=77) opted to enter the open-label EMPAVELI treatment period.
About the PADDOCK Study
PADDOCK (NCT02588833) was a multicenter, open-label, multiple ascending dose, Phase 1b study in 23 adults with paroxysmal nocturnal hemoglobinuria (PNH) who have never received eculizumab. The primary objective of this study, designed with two cohorts, was to establish the safety and efficacy of 270 mg of EMPAVELI administered daily by subcutaneous injection in adults with PNH. Patients in Cohort One received a suboptimal dose of 180 mg of EMPAVELI once daily for 28 days and subjects in Cohort Two received 270 mg of EMPAVELI once daily for up to one year.
About Empaveli™/Aspaveli® (pegcetacoplan)
Empaveli™/Aspaveli® (pegcetacoplan) is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. EMPAVELI is approved in the United States for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion for Aspaveli, which is the European trade name for pegcetacoplan, for the treatment of adults with PNH who are anemic after treatment with a C5 inhibitor for at least three months. The positive opinion from the CHMP is now referred to the European Commission for an approval decision. The therapy is also under investigation for several other rare diseases across hematology, nephrology, and neurology.
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.
- 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.
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.
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.
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.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is a rare, chronic, life-threatening blood disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria and difficulty breathing (dyspnea).
About the Apellis and Sobi Collaboration
Sobi and Apellis have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-US commercialisation rights for systemic pegcetacoplan, and Apellis has exclusive US commercialisation rights for systemic pegcetacoplan and retains worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA).
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. For more information, please visit http://apellis.com.
Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Sobi is providing sustainable access to innovative therapies in the areas of hematology, immunology and specialty indications. Today, Sobi employs approximately 1,500 people across Europe, North America, Middle East, and Asia. In 2020, Sobi’s revenues amounted to SEK 15.3 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube.
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