PharmaEssentia has commenced its Phase 3b clinical trial, named ECLIPSE PV, to investigate an accelerated dosing schedule of ropeginterferon alfa-2b-njft (BESREMi) in adult patients diagnosed with polycythemia vera (PV). This study, involving approximately 100 participants across the U.S. and Canada, seeks to determine if a more aggressive initial dosing of BESREMi can lead to quicker and more profound hematologic and molecular responses, potentially modifying the disease's progression and improving long-term control.
Trial Design and Objectives
The ECLIPSE PV trial is a randomized study comparing an accelerated dosing regimen of ropeginterferon alfa-2b-njft against the standard, currently labeled dosing. Participants will be randomized to either the accelerated arm (starting at 250 mcg, escalating to 350 mcg at week 2, and targeting 500 mcg at week 4, with subsequent adjustments based on tolerance) or the standard arm (starting at 50 or 100 mcg with 50 mcg titration every two weeks). The primary endpoint is the proportion of patients achieving a complete hematological response (CHR) at 24 weeks, defined by strict hematocrit, platelet, and leukocyte levels maintained for at least three months without phlebotomy. The study spans 48 weeks, followed by a 28-day safety follow-up, with responders eligible for a long-term extension phase.
Rationale for Accelerated Dosing
The rationale behind exploring an accelerated dosing schedule stems from the desire to achieve quicker disease control and potentially modify the underlying disease biology in PV. Polycythemia vera, a rare and chronic blood cancer driven by mutations in hematopoietic stem cells, leads to an overproduction of blood cells, elevating the risk of thrombosis, stroke, and heart attack. Current management strategies aim to control blood counts and alleviate symptoms, but the prospect of achieving deeper molecular responses with optimized dosing regimens is an area of active investigation.
Expert Commentary
According to John Mascarenhas, M.D., a professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, "This new study is addressing an important therapeutic and clinical question regarding whether treatment utilizing accelerated dosing leads to a more rapid hematologic and molecular response, indicating potential disease modifying activity and long-term disease control."
About Ropeginterferon Alfa-2b-njft (BESREMi)
Ropeginterferon alfa-2b-njft, marketed as BESREMi, is a monopegylated, long-acting interferon approved by the U.S. FDA in November 2021 for treating adults with PV. Its unique pegylation technology allows for less frequent administration, typically once every two weeks, offering flexible dosing to meet individual patient needs. BESREMi carries a boxed warning for the risk of serious disorders, including neuropsychiatric, autoimmune, ischemic, and infectious complications.
Polycythemia Vera: An Overview
Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an overproduction of red blood cells, often accompanied by increased white blood cell and platelet counts. The disease carries a risk of cardiovascular complications and transformation to myelofibrosis or acute leukemia. A common mutation driving PV is in the JAK2 gene. The initiation of the ECLIPSE PV trial represents a strategic effort to refine the therapeutic approach to PV, potentially offering improved outcomes for patients through optimized dosing strategies. Topline data from the trial are anticipated in 2024.
