MPN-469 Rusfertide (PTG-300) Treatment Interruption Reverses Hematological Gains and Upon Reinitiation, Restoration of Clinical Benefit Observed in Patients With Polycythemia Vera

Naveen Pemmaraju, Andrew Kuykendall, Marina Kremyanskaya, Yelena Ginzburg, Ellen Ritchie, Jason Gotlib, Aaron Gerds, Jeanne Palmer, Frank Valone, Paula O'Connor, Nishit Modi, Suneel Gupta, Ronald Hoffman, Srdan Verstovsek

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Polycythemia vera (PV) patients are routinely treated with periodic therapeutic phlebotomy (TP) alone or combined with cytoreductive therapy to maintain hematocrit (HCT) <45% and reduce the incidence of thrombosis. TP may not adequately control HCT and results in iron deficiency. Rusfertide, a hepcidin mimetic, eliminates phlebotomy requirements and improves iron deficiency. We examined the impact of rusfertide dosing interruption on TP requirements, HCT, and iron homeostasis in 2 studies during FDA-mandated clinical hold in response to pre-clinical and clinical safety findings. Design and Patients: The REVIVE study (NCT04057040), in phlebotomy-dependent PV patients consisted of 3 parts: (1) 28-week dose-finding; (2) 12-week blinded randomized withdrawal (1:1) rusfertide vs placebo; and (3) 52-week open-label extension. The PACIFIC study (NCT04767802) in PV patients with high HCT (>48%), consisted of 2 parts, (1) Induction with 40mg SQ twice weekly until HCT<45%, and (2) Continuation, typically with weekly dosing. Interventions: Subcutaneous rusfertide 10-120 mg weekly added to the existing regimen and adjusted to maintain HCT <45%. During treatment interruption, patients received their baseline cytoreductive regimens with TP to maintain HCT <45%. Main Outcome Measures: Iron homeostasis, HCT control, and TP requirements. Results: In the REVIVE study, all participants were essentially phlebotomy free, HCTs maintained at <45%, and ferritin normalized, when rusfertide was added to their treatment. In the PACIFIC study, participants with an average baseline HCT of 51% had their HCT reduced to and maintained at <45% within ~6 weeks of treatment initiation. When a clinical hold necessitated rusfertide dosing interruption, participants had significant (p<0.01) increases in TPs, HCT, and RBC count, and a decrease in serum ferritin. Reinitiating rusfertide normalized hematologic parameters, eliminated TP, and restored ferritin demonstrating the potential effectiveness of rusfertide. Most adverse events (AEs) were grade 1-2. The most frequent AEs were transient injection site reactions reported in 59% of participants. Conclusions: Rusfertide maintains HCT at <45%, essentially eliminates TP requirements, and reverses iron deficiency in PV patients with/without cytoreductive agents. Reversal of hematological parameters during dosing interruption further confirms the effect of rusfertide on erythrocytosis and iron homeostasis. A global Phase 3 trial, VERIFY (NCT05210790), has been initiated.

Original languageEnglish (US)
Pages (from-to)S338-S339
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • erythrocytosis
  • fatigue
  • hepcidin mimetic
  • MPN
  • polycythemia vera
  • rusfertide

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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