Treatment with APL-2 in eculizumab-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) resulted in broad control of hemolysis and normalization of mean hemoglobin to 12.2 g/dL by day 85, an increase of 4.2 g/dL from baseline
Previously transfusion-dependent patients did not require any transfusions during maintenance treatment with APL-2
Rapid and durable normalization Lactate Dehydrogenase, Reticulocyte Count and Total Bilirubin was achieved
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 interim data from its Phase 1b study of APL-2 in treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). Data from the PADDOCK trial were presented in a poster session today at the 60th Annual Meeting of the American Society of Hematology (ASH).
Interim results from the ongoing PADDOCK study evaluating 270mg subcutaneous APL-2 administered daily are presented. Data are presented for 19 patients at baseline, 15 patients on therapy at day 85 and 10 patients at day 169.
“There remains a significant unmet need in PNH driven by extravascular hemolysis, which is not addressed by C5 inhibitors such as eculizumab,” said Dr. Cedric Francois, MD, PhD, Apellis co-founder and CEO. “A recent large study showed that over 70% of PNH patients continue to be anemic and nearly 40% had at least one transfusion in the prior year while on treatment with eculizumab, the only approved therapy for PNH. 1 The study also showed that nearly all patients on eculizumab have reticulocytosis with an average of 1.9x the upper limit of normal (ULN). In our PADDOCK study, patients achieved transfusion independence with an average hemoglobin increase of 4.2 g/dL by day 85 to 12.2 g/dL and average reticulocytes decrease of 50% from 2.0x ULN to 1.0x ULN. LDH was reduced from 9.7x ULN at baseline to 0.9x at day 85 with 80% of patients achieving normal LDH. We could not be happier with these results as they show APL-2 represents a promising potential improvement in treatment options for PNH patients.”
These data will be presented by Dr. Raymond SM Wong of the Department of Medicine & Therapeutics, Prince of Wales Hospital at The Chinese University of Hong Kong. Professor Wong is a principal investigator for the PADDOCK study.
“APL-2 shows meaningful improvement in hematological parameters in ways not seen with standard of care C5 inhibition,” said Dr. Raymond Wong. “The hemoglobin increases and transfusion avoidance are highly meaningful, as is the broader hematological correction, including reticulocytes and bilirubin. The safety is also promising and the subcutaneous route of administration is friendlier to patients.”
Poster Presentation 1: Inhibition of C3 with APL-2 Results in Normalization of Markers of Intravascular and Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Session Name: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II
Date: Sunday, December 2, 2018
Presentation Time: 6:00 PM - 8:00 PM
Location: San Diego Convention Center, Hall GH
PADDOCK is an open-label, dose-escalation trial designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of multiple doses of APL-2, in patients with PNH, a rare and serious condition affecting the bone marrow. Data to be presented demonstrates:
Hemoglobin: Broad control of hemolysis, both intravascular and extravascular, led to significant and sustained increases in hemoglobin in the absence of transfusions. The baseline Hb was 8.0 g/dL (n=19) which increased to 10.8 g/dL (n=19) and 12.2 g/dL (n=15) at Days 29 and 85, respectively. In the 12 months prior to screening, subjects received an average of 8.7 units pRBCs (range 0-28). Transfusion independence was achieved while on APL-2 maintenance therapy with the exception of one patient with severe aplastic anemia at Day 364
Hemolysis Control: Systemic inhibition of C3 with APL-2 controls both intravascular and extravascular hemolysis in PNH patients as demonstrated by rapid and durable normalization of LDH, total bilirubin, and reticulocytes, all markers of hemolysis
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). To date, APL-2 has generally been well-tolerated. No significant infections have been observed in trials involving the systemic administration of APL-2, including the trials in PNH, AIHA or other trials.
In hematologic diseases, Apellis is currently evaluating APL-2 in two Phase 1b trials (PHAROAH and PADDOCK) for systemic administration in paroxysmal nocturnal hemoglobinuria (PNH). 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 3 trial for patients with PNH. For additional information regarding our clinical trials, visit www.apellis.com/clinical-trials.html.
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 about Apellis and APL-2, please visit http://www.apellis.com.
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 such as the results reported in this release 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; whether the results of such clinical trials will warrant regulatory submissions and whether APL-2 will receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies for GA, PNH or any other indication; 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 13, 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.