Results from the Phase 3 PERSIST-2 clinical trial of the investigational JAK2 inhibitor pacritinib have been published online in The Journal of the American Medical Association (JAMA) Oncology
. The data were originally presented at the 59th American Society of Hematology (ASH) Meeting
in December 2017.
In March 2015, CTI BioPharma announced that the Phase 3 PERSIST-1 trial met its primary endpoint when enrolled patients achieved a 35% or greater reduction in spleen volume reduction (SVR) versus physician-specific best available therapy (BAT). PERSIST-2 compared the safety and efficacy of pacritinib at 2 dose levels, compared to BAT, which included JAK1/JAK2 inhibitor ruxolitinib, in patients with myelofibrosis and thrombocytopenia.
Myelofibrosis and thrombocytopenia are two of the three main types of closely related groups of progressive blood cancers known as myeloproliferative neoplasms (MPNs). The former is a hematologic malignancy characterized by abnormal enlargement of the spleen, or splenomegaly, and debilitating symptoms. The latter is a poor prognostic feature and limits use of ruxolitinib.
The combined pacritinib arms (400 mg once daily and 22 mg twice daily) exhibited a significant improvement of 35% or more in SVR at 24 weeks of treatment in 27 of the 149 enrolled patients (18%) compared to 2 patients (3%) out of 72 patients in the BAT arm, which included treatment with ruxolitinib. Additionally, the combined pacritinib treatment arms demonstrated a greater than 50% reduction in total symptom score (TSS) in 37 patients (25%), versus 10 patients (14%) in the BAT arm.
"Pacritinib was shown to reduce both spleen volume and total symptom score, two very important clinical measures, in myelofibrosis patients with thrombocytopenia including those patients who received prior treatment with ruxolitinib," stated John Mascarenhas, M.D., Adult Leukemia Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in a press release
. "Clinical improvements in hemoglobin levels and reduction in transfusions were also seen in patients who received pacritinib, and pacritinib had a generally manageable safety profile."
Safety and tolerability were evaluated from the time of informed consent through the last day of study participation. Pharmacokinetics of pacritinib were characterized to evaluate exposure and exposure-response relationships. The JAK2 inhibitor was generally well tolerated, with the most commonly reported nonhematologic adverse events (AEs) occurring in less than 15% of patients and including: gastrointestinal (GI) events, fatigue, peripheral edema, and dizziness.
The rate of on-study death was lowest with pacritinib twice daily (6%) compared to BAT (9%) and pacritinib once daily (14%). Cardiac events and bleeding events were both reported at similar rates in all arms.
“These study results indicate there is important potential clinical benefit of pacritinib for these patients,” said Dr Mascarenhas.
According to the MPN Research Foundation
, approximately 30,000 people in the United States have been diagnosed with one of the three variations. The average survival for high-risk myelofibrosis patients is less than 18 months.
CTI BioPharma is currently enrolling patients in the PAC203 study, which will evaluate the safety and efficacy of three new dosing schedules of pacritinib, including 200 mg twice daily (BID), 100 mg twice daily (BID), and 100 mg once daily (QD).
For more information on MPNs, visit Rare Disease Report
’s MPN Condition Center
. For the latest on MPNs, follow RDR