Positive results from pacritinib Phase 3 trial for treatment of myelofibrosis presented at ASCO 2015

CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) and Baxter International's Bioscience business (NYSE: BAX) today announced data from PERSIST-1 – a randomized Phase 3 registration-directed trial examining pacritinib for the treatment of myelofibrosis – in a late-breaking oral session at the 51^st Annual Meeting of the American Society of Clinical Oncology (ASCO), May 29-June 2, 2015 in Chicago, Ill. Pacritinib is an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3. Data presented at ASCO (Abstract #LBA7006) show that compared to best available therapy (exclusive of a JAK inhibitor), pacritinib therapy resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms. Data were also selected for inclusion in the official ASCO Press Program.

"Myelofibrosis is a difficult-to-treat, rare chronic blood cancer in need of new options that can help overcome the many unique and burdensome symptoms that patients with this disease face on a regular basis, such as blood transfusions and debilitating pain and fatigue," 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. "Based on data showing improvement in bone marrow function, pacritinib may have the potential to modify disease in the sickest patients as monotherapy and warrants further evaluation in combination with other potential disease-modifying agents."

Myelofibrosis is associated with significantly reduced quality of life and shortened survival. Spleen enlargement (splenomegaly) is a common and debilitating symptom of myelofibrosis. As the disease progresses, the body slows production of important blood cells and within one year of diagnosis the incidence of disease-related thrombocytopenia (very low blood platelet counts), severe anemia, and red blood cell transfusion requirements increase significantly.

PERSIST-1 Findings Presented at ASCO
PERSIST-1 is a randomized (2:1), controlled Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to best available therapy (BAT) – which included a range of currently utilized off-label treatments – in 327 patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis), regardless of the patients' platelet counts. At study entry, 46 percent of patients were thrombocytopenic; 32 percent of patients had platelet counts less than 100,000 per microliter (<100,000/uL); and 16 percent of patients had platelet counts less than 50,000 per microliter (<50,000/uL); normal platelet counts range from 150,000 to 450,000 per microliter. The median duration of treatment was 16.2 months in patients treated with pacritinib, compared to 5.9 months in patients treated with BAT. The majority (79 percent) of patients on the BAT arm eventually crossed over to receive pacritinib therapy.

As previously reported, the trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan) in the intent-to-treat population (ITT). These results included patients with severe or life-threatening thrombocytopenia. Data presented at ASCO show that when measuring the volume of spleen reduction, the greatest difference in treatment arms was observed in evaluable patients with the lowest platelet counts (<50,000/uL platelets) (33.3 percent with pacritinib vs 0 percent with BAT) (p=0.037).

Beyond the statistically significant reductions in spleen volume, patients treated with pacritinib also experienced a sustained improvement in myelofibrosis-associated symptoms or Total Symptom Score (TSS) as measured by the Myeloproliferative Neoplasm Symptom Assessment Form electronic diary (MPN-SAF TSS and MPN-SAF TSS 2.0). The patient-reported outcomes instrument captures in an electronic diary how a patient feels or functions in relation to their health condition or treatment, including: fatigue, concentration, early satiety/fullness, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. When measuring the secondary endpoint (the proportion of patients with a 50 percent or greater reduction in TSS from baseline to Week 24), patients treated with pacritinib experienced greater improvement in their symptoms when compared to BAT, regardless of their baseline platelet counts (ITT patient population: 24.5 percent of pacritinib-treated patients vs 6.5 percent of BAT-treated patients) (p<0.0001); Evaluable patient population: 40.9 percent of pacritinib-treated patients vs 9.9 percent of BAT-treated patients) (p<0.0001).

Twenty-five percent (25%) of patients treated with pacritinib who were severely anemic and transfusion dependent – requiring at least six units of blood in the 90 days prior to study entry – became transfusion independent, compared to zero patients treated with BAT (p<0.05). Among patients with the lowest baseline platelets (<50,000/uL) who received treatment with pacritinib, a significant increase in platelet counts was observed over time compared to BAT (p=0.003) – with a 35 percent increase in platelet counts from baseline to Week 24.

The most common adverse events, occurring in 10 percent or more of patients treated with pacritinib within 24 weeks, of any grade, were: mild to moderate diarrhea (53.2 percent vs 12.3 percent with BAT), nausea (26.8 percent vs 6.6 percent with BAT), anemia (22.3 percent vs 19.8 percent with BAT), thrombocytopenia (16.8 percent vs 13.2 percent with BAT), and vomiting (15.9 percent vs 5.7 percent with BAT). Of the patients treated with pacritinib, 3 discontinued therapy and 13 patients required dose interruption (average one week) for diarrhea. Patients received a daily full dose of pacritinib over the duration of treatment. Gastrointestinal symptoms typically lasted for approximately one week and few patients discontinued treatment due to side effects. There were no Grade 4 gastrointestinal events reported.

"Results from PERSIST-1 add to the growing body of data showing the potential for pacritinib to address an unmet medical need that currently exists for patients with myelofibrosis, particularly patients with severely low platelet counts that result either from their disease or as a side effect from current treatment," said James A. Bianco, M.D., CTI BioPharma's President and CEO. "Based on the results observed in this trial, we are continuing to advance the broad clinical development program for pacritinib across a range of hematologic malignancies."

"PERSIST-1 is the most inclusive randomized study of patients with myelofibrosis ever conducted, as we believe it is truly representative of healthcare providers' real-world clinical experience, including patients with advanced disease, severe cytopenias, and a broad range of platelet count levels with the greatest need for effective treatment options," said David Meek, Head of Oncology at Baxter BioScience. "We look forward to advancing the clinical trial program of pacritinib for the treatment of myelofibrosis and to sharing these data with regulatory authorities."