Agency notes cases of intracranial hemorrhage, cardiac failure, and cardiac arrest
Previously, CTI BioPharma Corp. described a partial clinical hold issued on February 4 by the FDA regarding clinical studies being conducted under an investigational new drug (IND) application for the myelofibrosis treatment pacritinib. Now CTI BioPharma reports that studies of pacritinib have been placed on full clinical hold. The company has withdrawn its new drug application for pacritinib until it has had a chance to review safety and efficacy data from the phase III PERSIST-2 trial and decide its next steps.
In a February 8 letter, the FDA noted that the interim overall survival results from PERSIST-2 showed a detrimental effect on survival consistent with results from PERSIST-1. The deaths in PERSIST-2 in pacritinib-treated patients involved intracranial hemorrhage, cardiac failure, and cardiac arrest. The FDA’s latest recommendations supersede its recommendations in connection with the partial clinical hold imposed on February 4. The current recommendations include conducting dose-exploration studies for pacritinib in patients with myelofibrosis; submitting final study reports and datasets for PERSIST-1 and PERSIST-2; providing certain notifications; revising relevant statements in the related investigator’s brochure and informed consent documents; and making certain modifications to study protocols.
Under the full clinical hold, all patients currently receiving pacritinib must discontinue treatment immediately, and no patients can be enrolled in a pacritinib trial or start pacritinib as initial or crossover treatment.
Pacritinib is an oral tyrosine kinase inhibitor with activity against two activating mutations: Janus-associated kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. Activating mutations of JAK2 are implicated in certain blood-related cancers, including myeloproliferative neoplasms, leukemia, and certain solid tumors. FLT3 is a gene commonly found mutated in patients with acute myeloid leukemia. Pacritinib has undergone phase I and phase II studies in patients with myelofibrosis.
Sources: BioSpace(link is external); February 10, 2016; and CTI BioPharma(link is external); 2016.
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