PTG-300 Eliminates the Need for Therapeutic Phlebotomy in Both Low and High-Risk Polycythemia Vera Patients

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.33-35
• Main Authors: Kremyanskaya, Marina, Ginzburg, Yelena, Kuykendall, Andrew T., Yacoub, Abdulraheem, Yang, Jay, Gupta, Suneel K, Valone, Frank, Khanna, Sarita, Verstovsek, Srdan, Hoffman, Ronald
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-137285

Background. Polycythemia vera (PV) patients are treated with periodic therapeutic phlebotomy (TP) in order to maintain hematocrit levels 45%, thereby potentially increasing their risk of thrombosis. Symptomatic iron deficiency represents a challenge in PV as it is commonly present at diagnosis [Ginzburg Leukemia 2018] and worsens after repeated and/or frequent TP, and often symptomatic from their iron deficiency. We hypothesized that both iron deficiency and expanded erythropoiesis in PV lead to suppression of hepcidin, the body’s main negative regulator of iron metabolism, and that hepcidin suppression enhances iron absorption and availability for enhanced erythropoiesis in TP-requiring PV patients. We previously demonstrated that PTG-300, a hepcidin-mimetic, caused dose-related anemia in preclinical studies. In a phase 2 trial in β-thalassemia, PTG-300 leads to a sustained (3-7 days) decrease in serum iron and transferrin saturation (TSAT) but did not demonstrate off-target effects. The current study aims to compare the iron status and phlebotomy requirements in high TP-requiring PV patients before and during treatment with PTG-300 (Figure 1). Methods. PTG-300-04 is a 3-part Phase 2 trial consisting of (1) a 28-week dose-finding; (2) a 12-week blinded randomized withdrawal (1:1) PTG-300 vs placebo; and (3) a 52-week open label extension (Figure 1). Eligibility criteria include PV diagnosis (by 2016 WHO criteria) and ≥3 phlebotomies with or without concurrent cytoreductive therapy to maintain hematocrit ≤45% in the 24 weeks prior to enrollment. PTG-300 doses of 10, 20, 40, 60 and 80 mg administered subcutaneously weekly were adjusted to maintain hematocrit