Apellis Reports Pegcetacoplan Demonstrates Greater Treatment Responses and Quality-of-Life Improvements Compared to C5 Inhibitors for PNH
- Data were presented at the American Society of Hematology (ASH) Annual Meeting
- In an analysis from the 16-week Phase 3 PEGASUS study, 70.7% of patients treated with pegcetacoplan compared to 5.1% of eculizumab-treated patients achieved a good, major, or complete hematologic response based on published classifications
- Quality-of-life substantially improved for pegcetacoplan-treated patients, reaching near-normal levels on several measures, and did not change for eculizumab-treated patients in a PEGASUS analysis at 16 weeks
- A matching-adjusted indirect comparison suggests that 76% more patients on pegcetacoplan achieved hemoglobin stabilization and 71% more patients on pegcetacoplan were transfusion free compared to ravulizumab, a long-acting C5 inhibitor
WALTHAM, Mass., Dec. 07, 2020 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) today announced new analyses from the Phase 3 PEGASUS study, which demonstrated statistically significant improvements in treatment responses and substantial quality-of-life improvements with pegcetacoplan, an investigational, targeted C3 therapy, versus eculizumab, a C5 inhibitor, for paroxysmal nocturnal hemoglobinuria (PNH) at 16 weeks. Additionally, a matching-adjusted indirect comparison (MAIC) showed improvements in clinical, hematologic, and quality-of-life outcomes in patients treated with pegcetacoplan compared to ravulizumab, a long-acting C5 inhibitor. The data were presented at the virtual American Society of Hematology Annual Meeting (ASH) taking place December 5 - 8, 2020.
Substantial Improvements in Hematologic Responses and Quality-of-Life Demonstrated in Patients Treated with Pegcetacoplan Compared to Eculizumab
In an analysis of hematologic responses from the PEGASUS study, using response classifications developed independently by PNH experts that were published in Frontiers in Immunology,1 the findings showed:
- Approximately 70.7% of pegcetacoplan-treated patients (29/41) compared to 5.1% of eculizumab-treated patients (2/39) achieved a good, major, or complete hematologic response (p<0.0001), which means the individual treated with pegcetacoplan reached a level of mild or no anemia and did not require transfusions.
- 39% of patients treated with pegcetacoplan (16/41) compared to 0% of patients treated with eculizumab (0/39) achieved a complete response (p<0.0001), meaning they were transfusion free, experienced stable hemoglobin and lactate dehydrogenase (LDH) in the normal range, and showed no evidence of hemolysis based on LDH levels and reticulocyte count.
In a PEGASUS analysis of quality-of-life:
- Quality-of-life substantially improved for patients treated with pegcetacoplan, reaching near-normal levels on scales with a population norm, while no change was seen for eculizumab-treated patients. All scores were comparable at baseline across measures.
“Many PNH patients treated with C5 inhibitors still suffer from a significant disease burden, including frequent transfusions and debilitating fatigue, which reinforces the urgent need for new treatments,” said Brian Mulherin, M.D., PEGASUS study investigator and hematologist at St. Vincent Health Services. “The data presented at ASH show that pegcetacoplan, a targeted C3 therapy, demonstrate substantial and clinically meaningful improvements across a range of important hematologic measures compared to C5 inhibition.”
MAIC Found Greater Improvements in Hemoglobin Stabilization, Transfusion Avoidance, and Fatigue with Pegcetacoplan Versus Ravulizumab
Using an MAIC methodology, individual patient data from the PEGASUS study were compared to aggregate, published results from the ALXN1210-PNH-302 study, which compared ravulizumab and eculizumab among patients with PNH who previously were treated with eculizumab.
Detailed findings suggest:
- 76% more patients treated with pegcetacoplan achieved hemoglobin stabilization compared to ravulizumab, a long-acting C5 inhibitor.
- 71% more patients treated with pegcetacoplan were transfusion free compared to ravulizumab.
- In mean change from baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, pegcetacoplan showed an adjusted difference of nine points versus ravulizumab, suggesting pegcetacoplan is associated with an improvement that greatly exceeds the three-point threshold generally considered to be clinically meaningful.
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
“Along with positive changes in hemoglobin, we are seeing major improvements in fatigue and other quality-of-life measures in patients treated with pegcetacoplan compared to C5 inhibition,” said Federico Grossi, M.D., chief medical officer at Apellis. “These data show that the hematologic and clinical improvements demonstrated by pegcetacoplan have the potential to translate into meaningful outcomes for patients.”
Marketing applications for pegcetacoplan for the treatment of PNH were accepted by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The target date for the FDA decision is May 14, 2021, and an opinion from the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) is expected in 2021.
About the PEGASUS Study
The PEGASUS study (APL2-302; NCT03500549) is a multi-center, randomized, active-comparator controlled 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 pegcetacoplan 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 pegcetacoplan 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 pegcetacoplan 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 pegcetacoplan treatment period.
About the Matching-Adjusted Indirect Comparison (MAIC) Analysis
Using a matching-adjusted indirect comparison (MAIC) methodology, individual patient data from the PEGASUS study were compared to aggregate, published results from the ALXN1210-PNH-302 study,4 which compared the C5 inhibitors ravulizumab and eculizumab among patients with PNH who were previously treated with eculizumab. To adjust for cross-study differences in baseline characteristics, propensity score weighting was used to balance demographic and clinical characteristics. Outcomes assessed from the PEGASUS study at week 16 and the ALXN1210-PNH-302 study at week 26 included transfusion avoidance, number of units transfused, hemoglobin stabilization, and change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. As with other MAIC analyses, matching may not adjust for all confounding factors due to differences inherent in study design and entry criteria.
About Pegcetacoplan
Pegcetacoplan is an investigational, 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. Pegcetacoplan is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b. Pegcetacoplan is being evaluated in several clinical studies across hematology, ophthalmology, nephrology, and neurology. Marketing applications for pegcetacoplan for paroxysmal nocturnal hemoglobinuria (PNH) are under review by the U.S. Food and Drug Administration (FDA), which has granted the application Priority Review designation, and the European Medicines Agency (EMA). Pegcetacoplan was also granted Fast Track designation by the FDA for the treatment of geographic atrophy and received orphan drug designation for the treatment of C3 glomerulopathy by the FDA and EMA. For additional information regarding pegcetacoplan clinical trials, visit .
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). A retrospective analysis shows that, even on eculizumab, approximately 72% of people with PNH have anemia, a key indicator of ongoing hemolysis.5 The analysis also finds that 36% of patients require one or more transfusions a year and 16% require three or more.5
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. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and retains worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy (GA).
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. For more information, please visit .
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. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. 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, including: whether the company’s clinical trials will be fully enrolled and completed when anticipated; whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the company’s clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA, PNH, CAD, C3G, IC-MPGN, ALS or any other indication when expected or at all; whether, if Apellis’ products receive approval, they will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 2, 2020 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.
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1. Risitano AM, Marotta S, Ricci P, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
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.
4. Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549.
5. McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.
