CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) and Baxter International Inc. (NYSE: BAX) today announced positive top-line results for the primary endpoint from PERSIST-1, the randomized, controlled Phase 3 registration clinical trial examining pacritinib, a next generation oral JAK2/FLT3 multikinase inhibitor, for the treatment of patients with primary or secondary myelofibrosis. The PERSIST-1 trial met its primary endpoint in the intent-to-treat population with statistically significant activity observed in patients irrespective of their initial platelet count, including patients with very low platelet counts at study entry, a condition known as severe or life-threatening thrombocytopenia.
The primary endpoint of the trial was the proportion of patients achieving a 35 percent or greater reduction in spleen volume from baseline to Week 24 as measured by magnetic resonance imaging (MRI) or computerized tomography (CT) when compared with physician-specified best available therapy (BAT), excluding treatment with JAK2 inhibitors. The PERSIST-1 trial demonstrated that pacritinib treatment provided a clinically and statistically significant response rate (p = 0.0003) in spleen volume reduction in patients with myelofibrosis when compared to BAT. Importantly, the trial results also demonstrated a significant difference among patients with platelet counts of less than 100,000 per microliter and less than 50,000 per microliter, both subgroups that were stratified at randomization. The magnitude of treatment effect was consistent with previously reported Phase 2 results, with the greatest reduction observed among the sickest patients (platelet counts <50,000 per microliter). Among 50 patients who were red blood cell (RBC) transfusion dependent at study entry (≥ 6 units of RBC over 90 days pre entry), pacritinib therapy resulted in a clinically meaningful percentage of patients becoming transfusion independent compared to BAT. Seventy-nine percent (79%) of patients in the BAT arm of the study crossed over to pacritinib therapy.
The safety profile in the PERSIST-1 trial was consistent with prior Phase 2 trials. While the most common treatment emergent adverse events were diarrhea, nausea and vomiting, the incidence of grade 3 events was lower than observed in Phase 2 trials. No grade 4 gastrointestinal adverse events were reported. Three patients discontinued therapy and nine patients required dose reduction for diarrhea. Preliminary analysis suggests that very few patients discontinued treatment while on pacritinib or required a dose reduction due to treatment-related anemia or thrombocytopenia. Additional data from ongoing analyses along with top-line results from PERSIST-1 will be submitted for presentation at an upcoming scientific meeting.
"Despite the introduction of JAK2 inhibitors as effective therapies for patients with myelofibrosis, there remains a treatment gap for patients with disease-related or treatment emergent thrombocytopenia. The currently approved drug may require dose titration to less effective doses in this patient population, thus limiting our ability to effectively treat them. Results from the PERSIST-1 randomized trial demonstrate that pacritinib could address this unmet medical need," stated Claire Harrison, M.D., Consultant Hematologist, Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital, London, United Kingdom and one of the principal investigators for PERSIST-1. "It is encouraging to see that patients were able to receive therapeutic doses of pacritinib over a long period of time irrespective of their baseline platelet or red blood cell count while having therapeutic benefit in reduction in spleen volume and disease-related symptoms and improvement in transfusion dependency."
"PERSIST-1 is the first randomized Phase 3 trial investigating the potential benefit of a JAK2 inhibitor across a patient population with myelofibrosis that is representative of patients that healthcare providers see and treat in clinical practice," said James A. Bianco, M.D., CTI BioPharma's President and CEO. "We are excited by the clinical profile demonstrated in this randomized trial with respect to benefit–risk especially for a segment of MF patients excluded from other randomized trials with JAK2 inhibitors. We are grateful for the support and commitment of the investigators, our steering committee and, most importantly, all the patients who participated in PERSIST-1. We look forward to building on the progress we have made thus far."
"These positive top-line results illustrate the potential of this investigational treatment to become a valuable new treatment option for this challenging disease. Pacritinib is an important component of Baxter's growing oncology portfolio, and we look forward to partnering with CTI BioPharma to share these results with physicians and discussing next steps with regulatory agencies," said David Meek, Head of Oncology at Baxter BioScience.