Session: 102. Regulation of Iron Metabolism: Poster II
Hematology Disease Topics & Pathways:
Adult, Diseases, Non-Biological, Therapies, Biological Processes, Polycythemia vera, erythropoiesis, Study Population, Myeloid Malignancies, Clinically relevant, iron metabolism, iron transport
Methods. Polycythemia patients who met 2016 WHO criteria for diagnosis were enrolled in the 28-week dose finding part of a Phase 2 trial. All patients required ≥3 phlebotomies with or without concurrent cytoreductive therapy over 6 months prior to enrollment. Patients were given PTG-300 doses of 10, 20, 40, 60 and 80 mg administered subcutaneously weekly in individualized adjustment to maintain hematocrit <45%. Body iron status was quantified by monitoring serum ferritin, serum iron, transferrin saturation (TSAT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
Results. Thirteen subjects were enrolled to date: 7/13 with low risk, mean age 57.4 years (range 31-74). Six receiving TP alone, 6 on concurrent hydroxyurea, 1 on concurrent interferon; TP in the 24 weeks prior to enrollment = 3-9; median time between TP = 42 days. All subjects-maintained hematocrit <45% after appropriate dose adjustment. Mean baseline values were serum ferritin = 14.2 ng/mL (5, 37); serum iron = 33.0 ug/dL (16.8, 107.8); and TSAT = 7.6% (4, 30). During treatment with PTG-300, serum ferritin levels increased progressively toward normal (Figure 1a) reflecting increase in iron stores. TSAT (Figure 1b) and serum iron values increased modestly but remained below normal ranges, reflecting PTG-300’s pharmacodynamic effect of inhibiting iron release from intracellular stores. This was associated with increased MCV (Figure 1c) and MCH (Figure 1d) and decreased hematocrit and erythrocyte counts, together suggesting a normalization of iron distribution.
Conclusions. The current results indicate that PTG-300 is an effective agent for the controlling hematocrit and reversing iron deficiency. The effect of PTG-300 on PV-related symptoms and those of iron deficiency, are also being evaluated. Continued patient enrollment will enable more definitive conclusions regarding the efficacy and safety of hepcidin mimetic PTG-300 in PV patients with high TP requirements.
Disclosures: Kremyanskaya: Incyte Corporation: Research Funding; Bristol Myers Squibb: Research Funding; Astex Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Protagonist Therapeutics: Consultancy, Research Funding. Kuykendall: Novartis: Research Funding; Blueprint Medicines: Research Funding; BMS: Research Funding; Incyte: Research Funding. Yacoub: Agios: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara Therapeutics: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support. Yang: AROG: Research Funding; AstraZeneca: Research Funding; Jannsen: Research Funding; Protagonist: Research Funding. Gupta: Protagonist: Current Employment. Valone: Protagonist: Current Employment. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. Hoffman: Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Dompe: Research Funding; Forbius: Consultancy; Protagonist: Consultancy. Verstovsek: Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; Protagonist Therapeutics: Research Funding; NS Pharma: Research Funding; CTI Biopharma Corp: Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; PharmaEssentia: Research Funding; Roche: Research Funding; AstraZeneca: Research Funding.