The U.S. Food and Drug Administration (FDA) pulled the investigational new drug application for the JAK2 inhibitor pacritinib, halting the ongoing PERSIST-1 and PERSIST-2 clinical trials and affecting future planned clinical trials.
PERSIST-1 compared pacritinib with best-available treatment (including erythropoietin-stimulating agents, hydroxyurea, and immunomodulatory agents) in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. The PERSIST-2 trial evaluated pacritinib for patients with myelofibrosis whose platelet counts are ≤100,000/µL.
In their decision letter, the FDA noted that the interim overall survival results generated from the unblinded PERSIST-2 data show a detrimental effect on survival for patients treated with pacritinib, consistent with the results of PERSIST-1. There also was excess mortality in pacritinib-treated patients compared with the control arm in the PERSIST-1 trial after crossover to the pacritinib arm. The deaths in PERSIST-2 in pacritinib-treated patients include intracranial hemorrhage, cardiac failure, and cardiac arrest.
Effective immediately, all patients on pacritinib must discontinue treatment. New patients cannot be enrolled in the PERSIST trials, and enrolled patients cannot start pacritinib as either initial or crossover treatment. In addition, the FDA recommended that the CTI BioPharma (pacritinib’s manufacturer) make certain modifications of protocols, including modifying all protocols for randomized trials to disallow crossover to pacritinib, provide certain notifications, and revise relevant statements in the informed consent documents.
Source: CTI BioPharma news release, February 8, 2016.