Mixed results have been reported from a randomized, controlled, phase 3 trial comparing pacritinib (CTI BioPharma Corp.), an investigational oral multikinase inhibitor, with physician-specified best available therapy (BAT), including the approved Janus kinase 1 and 2 (JAK1/JAK2) inhibitor ruxolitinib (Jakafi, Incyte), for the treatment of patients with myelofibrosis whose platelet counts were less than 100,000/mcL––a patient population with high-risk advanced disease.
In the PERSIST-2 trial, patients with myelofibrosis were randomly assigned to receive pacritinib 200 mg twice daily, pacritinib 400 mg once daily, or BAT. Clinical studies of pacritinib are currently subject to a full clinical hold issued by the FDA in February 2016. The study was originally designed to enroll 300 patients to evaluate the study objectives. A total of 221 patients were enrolled at least 24 weeks before the full clinical hold and were potentially evaluable for efficacy. These patients comprised the population used to evaluate the study’s efficacy endpoints. The coprimary endpoints were the percentage of patients achieving a 35% or greater reduction in spleen volume, as measured by a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan, from baseline to week 24 of treatment, and the percentage of patients achieving a reduction in the Total Symptom Score (TSS) of 50% or greater using seven key symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to week 24. The study’s primary objective was to compare the pooled pacritinib arms with BAT.
Preliminary results demonstrated that the PERSIST-2 trial met one of the coprimary endpoints, showing a statistically significant response rate in spleen volume reduction (SVR) in patients with myelofibrosis treated with pacritinib compared with BAT, including the approved JAK2 inhibitor ruxolitinib (P <0.01). The trial did not meet the other coprimary endpoint of a reduction of greater than 50% in the TSS compared with BAT (P = 0.0791).
The most common treatment-emergent adverse events for pacritinib included diarrhea, nausea, and vomiting. The rates of cardiac and bleeding adverse events and the overall mortality rates were similar across treatment arms.
In February, the FDA placed studies of pacritinib on full clinical hold based on interim survival results from the pivotal PERSIST-2 trial. In that study, deaths resulting from intracranial hemorrhage, cardiac failure, and cardiac arrest were reported in pacritinib-treated patients.