CRESTWOOD, Ky., and WALTHAM Mass. -- Apellis Pharmaceuticals Inc., (Nasdaq:APLS) a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds to treat disease through the inhibition of the complement system, today announced that it has commenced its PEGASUS Phase 3 trial assessing the safety and efficacy of APL-2 in patients with paroxysmal nocturnal hemoglobinuria (PNH) compared to eculizumab (Soliris™). The development was highlighted at the end of Apellis’ R&D Day, where the company provided important clinical updates on its PNH program.
PNH is a rare, acquired, potentially life-threatening disease characterized by complement-mediated thrombosis and hemolytic anemia. Apellis is developing APL-2, a novel inhibitor of complement factor C3 as a next generation monotherapy, with the goal of improving anemia and transfusion dependency in patients with PNH. In a recent study, up to 70% of patients treated with eculizumab (the only currently approved therapy for PNH) were anemic with hemoglobin levels below 12.0 g/dL.1
PEGASUS is a 70-patient, randomized, head-to-head study comparing APL-2 monotherapy to eculizumab monotherapy in patients currently on treatment with eculizumab who have a hemoglobin level <10.5 g/dL, regardless of eculizumab dose or transfusion history. Patients will be co-treated for 4 weeks with subcutaneous injection twice weekly dosing of APL-2 with eculizumab and then randomized 1:1 to either APL-2 monotherapy or eculizumab monotherapy and monitored for 56 weeks. The primary endpoint will be the week 16 change from baseline in hemoglobin levels. Hemoglobin response is defined as a 1.0 g/dL increase in hemoglobin from baseline at week 16. Secondary endpoints include week 16 change from baseline in reticulocyte count, LDH levels and FACIT- Fatigue Score; number of PRBC (packed red blood cell) units transfused from week 4 to 16 and hemoglobin response in the absence of transfusions, and reticulocyte normalization in the absence of transfusion at week 16.
To date, subcutaneous APL-2 has generally been well-tolerated with cumulative systemic exposure of over 12 patient years of treatment on APL-2. No significant infections or thromboembolic events have been observed.
"The initiation of the first of our two Phase 3 trials for patients with PNH is a significant milestone for Apellis as we continue to advance the development of APL-2 for this indication,” said Dr. Cedric Francois, MD, PhD, Apellis co-founder and CEO. "We believe there’s an unmet medical need to bring patients with PNH a better treatment option that will provide broad hematological correction and better quality of life than the current standard of care.”
About Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening disease characterized by complement-mediated hemolysis with or without hemoglobinuria, an increased susceptibility to thrombotic episodes and/or some degree of bone marrow dysfunction. A significant subset of patients treated with the current standard of care still suffer from debilitating anemia and transfusion dependence.
APL-2 is designed to inhibit the complement cascade centrally at C3 and may have the potential to treat a wide range of complement-mediated diseases more effectively than is possible with partial inhibitors of complement. APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). In addition to the PEGASUS trial, Apellis is currently evaluating APL-2 in two Phase 1b clinical trials for systemic administration in paroxysmal nocturnal hemoglobinuria (the PHAROAH trial and the PADDOCK trial). Previously reported interim data from these trials showed improvements in lactate dehydrogenase and hemoglobin levels in patients who are suboptimal responders to eculizumab and untreated patients, respectively. Apellis is also testing APL-2 for systemic administration in a Phase 2 clinical trial in autoimmune hemolytic anemia (AIHA) and a Phase 2 clinical trial in complement dependent nephropathies, as well as a Phase 1b/2 clinical trial evaluating intravitreal APL-2 in wet age-related macular degeneration. Phase 3 studies are planned in intravitreal APL-2 for geographic atrophy (GA) and PNH. Future clinical studies of APL-2 are anticipated in other diseases in which complement is implicated.
Apellis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of a broad range of life-threatening or debilitating autoimmune diseases based upon complement immunotherapy through the inhibition of the complement system at the level of C3. Apellis is the first company to advance chronic therapy with a C3 inhibitor into clinical trials. For additional information our clinical trials visit www.apellis.com/clinical-trials.html.
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 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 APL-2 will successfully advance through the clinical trial process on a timely basis, or at all, and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; 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 April 30, 2018, 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.
1. McKinley CE, Richards SJ, Munir T, et al. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood (ASH Annual Meeting Abstracts) 2017;130(S1):3471.