CTI BioPharma Corp. and Baxalta Incorporated announced results from a new analysis of the pivotal phase 3 trial, PERSIST-1, evaluating pacritinib versus best available therapy, excluding treatment with JAK2 inhibitors (BAT), in patients with myelofibrosis.

Data examining patient outcomes across baseline demographic factors that are associated with prognosis – including age, baseline hemoglobin, baseline platelet count, ECOG status, JAK2 mutation status and red blood cell transfusion dependency – showed that treatment with pacritinib resulted in consistent rates of spleen volume reduction and control of disease-related symptoms across all intermediate or high-risk myelofibrosis subgroups. These findings were presented by Alessandro M. Vannucchi, M.D., associate professor of hematology, University of Florence, Italy, during an oral presentation at the 57th American Society of Hematology (ASH 2015) Annual Meeting and Exposition in Orlando.

Pacritinib is an investigational oral multikinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, which are kinases found to be involved in the growth and spread of myelofibrosis and other blood-related cancers such as acute myeloid leukemia (AML). In August 2014, pacritinib was granted Fast Track designation by the US Food and Drug Administration (FDA) for the treatment of intermediate and high-risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy.

CTI BioPharma and Baxalta are parties to a worldwide license agreement to develop and commercialise pacritinib. CTI BioPharma and Baxalta will jointly commercialise pacritinib in the US while Baxalta has exclusive commercialisation rights for all indications outside the US.

The companies recently announced the initiation of a rolling new drug application (NDA) to the FDA for pacritinib. The companies are seeking accelerated approval and priority review of pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/µL).

"Reducing the burden of myelofibrosis-related symptoms is an important goal of treatment. However, for patients diagnosed with this rare blood cancer, there are limited therapeutic options – a gap that is even more significant for patients with low platelet counts," said Prof. Vannucchi. "These data presented at ASH 2015 are important and clinically meaningful as they demonstrate pacritinib's potential to achieve treatment goals across intermediate or high-risk patients with myelofibrosis, regardless of baseline characteristics including starting platelet count."

Myelofibrosis is a rare blood cancer associated with significantly reduced quality of life and shortened survival. Most patients with the disease present with enlarged spleens (splenomegaly), as well as many other potentially devastating physical symptoms such as abdominal discomfort, bone pain, feeling full after eating little, severe itching, night sweats and extreme fatigue.

"The results from this analysis add to the growing body of data for pacritinib suggesting it is a unique JAK inhibitor with a differentiated efficacy and safety profile that is not limited by the baseline characteristics of patients with myelofibrosis," said James Bianco, M.D., president and chief executive officer, CTI BioPharma.

"We believe pacritinib has the potential to fill a gap that exists for many patients whose lives are profoundly impacted by myelofibrosis, particularly those patients with low platelet counts."

"We are developing pacritinib with particular focus on targeting the underlying biology of myelofibrosis to improve the treatment landscape for patients with this underserved, progressive disease, including those in intermediate and high-risk subgroups," said David Meek, executive vice president and president, oncology at Baxalta.

"We look forward to working with worldwide regulatory authorities to advance treatment options for all patients with myelofibrosis as we begin our registration submissions for pacritinib in the coming months."

Findings presented at ASH 2015 were based on the analysis of baseline patients' characteristics from PERSIST-1, a randomized phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT that included a broad range of currently utilized treatments. As previously reported, the trial met its primary endpoint of spleen volume reduction (35 per cent or greater from baseline to week 24 by MRI/CT scan) in the intent-to-treat population.

The subgroup analysis discussed above assessed results observed in patients achieving 35 per cent or greater spleen volume reduction from baseline or a decrease of 50 per cent or more in Total Symptom Score (TSS) by baseline characteristics or risk factors, including initial platelet count, JAK2V617F mutation status, red blood cell transfusions and bone pain. Findings showed that results (from the primary analysis) were consistent across all subgroups evaluated. Achievement of 35 per cent or greater spleen volume reduction was independent of most risk factors assessed and a 50 per cent or more decrease in TSS was independent of characteristics evaluated, except bone pain score greater than three at baseline.

The most common adverse events in the pacritinib arm vs. BAT that showed more than 5 per cent difference were diarrhea (57 per cent vs. 12 per cent), nausea (29 per cent vs. 6 per cent) and vomiting (19 per cent vs. 5 per cent). No Grade 4 gastrointestinal events were reported.

Also presented were patient-reported outcome data that examined the relationship between myelofibrosis-associated symptoms (based on the TSS) and changes in splenomegaly and health-related quality of life (HRQoL) outcomes in the PERSIST-1 overall patient population and in patients with baseline thrombocytopenia. The analysis showed TSS response was associated with improvements in spleen volume response and perceived overall health state; this trend was also observed in patients with low baseline platelet counts (<50,000/µL and <100,000/ µL). In all patient populations analysed, TSS response was significantly associated with improvements in fatigue, a major contributor to poor HRQoL in patients with myelofibrosis. Significant improvements in social functioning, appetite loss and insomnia were also observed in patients with baseline thrombocytopenia. These data were presented in a poster presentation by Ruben Mesa, M.D., Chair, Hematology and Medical Oncology Division, Mayo Clinic, Scottsdale.

PERSIST-1 is a randomized (2:1), controlled phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT – which included a broad range of currently utilised 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 per cent of patients were thrombocytopenic; 32 per cent of patients had platelet counts less than 100,000 per microliter (<100,000/µL); and 16 per cent of patients had platelet counts less than 50,000 per microliter (<50,000/µL); 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 per cent) of patients on the BAT arm eventually crossed over to receive pacritinib therapy.