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Apellis and Sobi Report New Data Reinforcing the Robust Efficacy and Safety Profile of EMPAVELI® (pegcetacoplan) for PNH at EHA 2022 Congress

June 10, 2022

WALTHAM, Mass. and STOCKHOLM, Sweden, June 10, 2022 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Sobi® (STO:SOBI) today reported new analyses of Phase 3 studies that reinforce the robust efficacy and safety profile of EMPAVELI®/Aspaveli® (pegcetacoplan) for paroxysmal nocturnal hemoglobinuria (PNH). The data will be presented at the hybrid European Hematology Association (EHA) Congress in Vienna, Austria.

New analyses demonstrated that treatment with EMPAVELI resulted in meaningful improvements in quality of life for treatment-naïve patients and suggested the incidence of thrombosis was comparable to eculizumab, a C5 inhibitor. Additionally, a matching-adjusted indirect comparison (MAIC) showed significant improvements in clinical outcomes in treatment-naïve patients who received EMPAVELI compared to C5 inhibitors.

“The data presented at EHA add to a growing body of evidence, which shows that EMPAVELI leads to both clinically meaningful efficacy and improved quality of life regardless of prior treatment,” said Peter Hillmen, M.B. Ch.B., Ph.D., head of hematology engagement at Apellis. “Many patients experience a significant disease burden, even with C5 inhibitor treatment, so these data further emphasize that EMPAVELI has the potential to become a new standard of care for PNH.”

“We are very pleased that these new data further reinforce the safety and efficacy of EMPAVELI/Aspaveli in treating such a rare, chronic, and life-threatening condition,” said Anders Ullman, head of research and development and chief medical officer at Sobi. “Sobi and Apellis are firmly committed to improving the care and quality of life for those affected by this rare blood disease.”

EMPAVELI Demonstrated Meaningful Improvements in Quality of Life in Treatment-Naïve Patients

In an analysis of the Phase 3 PRINCE study, EMPAVELI patients who were previously treatment-naïve demonstrated meaningful quality-of-life improvements through 26 weeks, reaching normal or near-normal levels of the general population. These data, which were assessed using multiple measures including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 scale, will be reported during an oral presentation at the congress.

Results Suggested Incidence of Thrombosis Comparable across EMPAVELI- and Eculizumab-Treated Patient Groups

A post hoc analysis of data from all PNH clinical trials of EMPAVELI revealed that there were 1.54 thrombotic events per 100 patient-years for EMPAVELI-treated patients compared to 1.77 thrombotic events per 100 patient-years for eculizumab-treated patients prior to entry in the Phase 3 PEGASUS study.

Additionally, D-dimer normalization was comparable across EMPAVELI- and eculizumab-treated patient groups in a post hoc analysis of the Phase 3 studies. D-dimer is a marker of thrombotic risk, one of the most common life-threatening complications of PNH.

EMPAVELI Demonstrated Significant Improvements in Clinical Outcomes Versus C5 Inhibitors in Treatment-Naïve Patients

Using a MAIC methodology, individual patient data from the Phase 3 PRINCE study were compared to aggregate, published data from the ALXN1210-PNH-301 study,1 which compared C5 inhibitors ravulizumab and eculizumab in PNH patients who were treatment naïve.

Patients treated with EMPAVELI showed significant improvements compared to C5 inhibitors across all key disease measures evaluated, including lactate dehydrogenase normalization, hemoglobin stabilization, and transfusion avoidance at Week 26.

In the absence of a clinical head-to-head study, MAIC is a valid and accepted method for comparative effectiveness research used by health technology assessment bodies across the world.2,3 As with other MAIC analyses, matching may not adjust for all confounding factors due to differences inherent in study design and entry criteria. Key limitations include differences in the route of administration, treatment administration schedule, and dosing regimen.

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. It is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in the United States, Australia, and Saudi Arabia as EMPAVELI and in the European Union and the United Kingdom as Aspaveli. The therapy is also under investigation for several other rare diseases across hematology, nephrology, and neurology.

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®/Aspaveli® (pegcetacoplan) in patients who had 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, open-label, 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®/Aspaveli® 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 Matching-Adjusted Indirect Comparison (MAIC) Analysis
Using a matching-adjusted indirect comparison (MAIC) methodology, individual patient data from the PRINCE study were compared to aggregate, published results from the ALXN1210-PNH-301 study,1 which compared the C5 inhibitors ravulizumab and eculizumab among patients with PNH who were naïve to complement inhibitor treatment. To adjust for cross-study differences in baseline characteristics, propensity score weighting was used to balance demographic and clinical characteristics. Outcomes assessed from the PRINCE study at week 26 and the ALXN1210-PNH-301 study at week 26 included lactate dehydrogenase (LDH) levels, LDH normalization, hemoglobin stabilization, and transfusion avoidance. As with other MAIC analyses, matching may not adjust for all confounding factors due to differences inherent in study design and entry criteria.

U.S. Indication and Important Safety Information for EMPAVELI

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


  • 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 pneumoniaeNeisseria 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 pneumoniaeNeisseria meningitidis, and Haemophilus influenzae


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 pneumoniaeNeisseria 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

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.

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%).

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 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
Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy.

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 complement, we ushered in the first new class of complement medicine in 15 years with the approval of the first and only targeted C3 therapy. We are advancing this science to continually develop transformative medicines for people living with rare, retinal, and neurological diseases. For more information, please visit or follow us on Twitter and LinkedIn.

About Sobi®
Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Providing sustainable access to innovative medicines in the areas of hematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East, and Asia. In 2021, revenue amounted to SEK 15.5 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at, LinkedIn and YouTube.

Apellis Forward-Looking Statement
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q with the Securities and Exchange Commission on May 4, 2022 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Media Contact: 
Lissa Pavluk 

Investor Contact: 
Meredith Kaya 

For details on how to contact the Sobi Investor Relations Team, click here. For Sobi Media contacts, click here.

1. Lee JW, Sicre de Fontbrune F, Wong Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):530-539. doi:10.1182/blood-2018-09-876136
2. Phillippo DM, Ades AE, Dias S, Palmer S, Abrams KR, and Welton NJ. Methods for Population-Adjusted Indirect Comparisons in Health Technology Appraisal. Medical Decision Making 2018;38(2): 200-211.
3. Signorovitch JE, Sikirica V, Erder MH, Xie J, Lu M, Hodgkins PS, Betts KA, and Wu EQ. Matching-Adjusted Indirect Comparisons: A New Tool for Timely Comparative Effectiveness Research. Value in Health 2012;15(6):940-947.