The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).
The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.
Both trials suggested pacritinib can be more effective than the best available therapy for MF.
However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.
Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.
When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.
CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial.
The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.
CTI BioPharma said it expects to start the trial in the second quarter of 2017.
“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.
“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”
