CTI BioPharma presents new anemia benefit data from pacritinib program

CTI BioPharma announced an oral presentation and two poster presentations from the company’s pacritinib program at the 64th American Society of Hematology Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10-13, 2022. A new post-hoc data analysis from the Phase 3 PERSIST-2 trial of pacritinib, a novel JAK2/IRAK1 inhibitor approved by the U.S. Food and Drug Administration for patients with myelofibrosis and severe thrombocytopenia, highlights pacritinib’s potential anemia benefit in patients with myelofibrosis through its inhibition of Activin A receptor type 1. Pacritinib demonstrated hemoglobin improvement in the randomized Phase 3 PERSIST-2 study, though the mechanism behind and the extent of pacritinib’s anemia benefit has not been fully described. A retrospective analysis of the Phase 3 PERSIST-2 study was performed to assess pacritinib’s in vitro potency against ACVR1 and its ability to reduce hepcidin and to describe the impact of pacritinib 200 mg BID on RBC transfusion independence. Results from in vitro testing suggest pacritinib is a potent ACVR1 inhibitor that reduces hepcidin expression. Analysis of the clinical data shows that pacritinib therapy results in transfusion independence in patients with myelofibrosis who require RBC transfusions. Given this unique mechanism of action, pacritinib may provide a therapeutic option that provides spleen, symptom and anemia benefits to patients with myelofibrosis. A retrospective analysis of baseline data from the Phase 3 PERSIST-1 and Phase 2 PAC203 trials was performed to describe the differential impact of thrombocytopenia and anemia on symptom burden by analyzing symptom data from patients with myelofibrosis who have isolated thrombocytopenia versus isolated anemia. Results showed that patients with isolated thrombocytopenia had more severe symptom burden than those with isolated anemia, particularly with physical function- and spleen-related symptoms. While amelioration of anemia is an important therapeutic goal for patients with cytopenic myelofibrosis, these data suggest that additional efforts aimed at the control of platelet count and underlying disease should be implemented to achieve optimal symptom control. Pacritinib is a novel JAK2/IRAK1/ACVR1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia. So far, treatment options for patients with myelofibrosis and severe thrombocytopenia are limited due to the high incidence of treatment-related thrombocytopenia when other JAK inhibitors are used. Previously, pacritinib demonstrated clinical activity in myelofibrosis in two Phase 3 studies — PERSIST-1 and PERSIST-2 — and a Phase 2 dose-finding study, all of which included patients with severe thrombocytopenia. PACIFICA is a multinational, multicenter, 2:1 randomized, controlled Phase 3 trial designed to confirm the efficacy and safety of pacritinib 200 mg twice daily vs physician’s choice therapy in patients with myelofibrosis and severe thrombocytopenia.