The US Food and Drug Administration (FDA) has placed a full clinical hold on trials conducted under the investigational new drug application for pacritinib, a JAK2/FLT3 inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis (MF).
The hold means all patients currently on pacritinib must stop taking the drug immediately, and no patients can be enrolled on a pacritinib trial or start pacritinib as initial or crossover treatment.
In addition, CTI BioPharma has withdrawn the new drug application for pacritinib while the company reviews data from the phase 3 PERSIST-2 trial.
The FDA’s decision to place a full clinical hold on pacritinib trials was due to interim results from PERSIST-2. The aim of this trial was to compare pacritinib to best available therapy in patients with thrombocytopenia and primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF.
The overall survival results from PERSIST-2 indicate that pacritinib had a detrimental effect on survival, which is consistent with results from the PERSIST-1 trial. The deaths in pacritinib-treated patients on PERSIST-2 include intracranial hemorrhage, cardiac failure, and cardiac arrest.
Based on these results, the FDA has made recommendations for CTI BioPharma that supersede the agency’s previous recommendations.
On February 4, 2016, the FDA placed a partial clinical hold on pacritinib trials and made related recommendations for CTI BioPharma, advising that the company modify trial protocols and take other actions in compliance with the partial clinical hold.
Now that pacritinib trials are on full clinical hold, the FDA is recommending that CTI BioPharma conduct dose exploration studies for pacritinib in patients with MF and submit final study reports and datasets for PERSIST-1 and PERSIST-2.
The FDA is also recommending that CTI BioPharma provide certain notifications, revise relevant statements in the related investigator’s brochure and informed consent documents, make certain modifications to protocols, and request a meeting with the FDA prior to submitting a response to the full clinical hold.
CTI BioPharma said all clinical investigators worldwide have been notified of the hold.
