The investigative agent, pacritinib, being evaluated for treatment of myelofibrosis has been placed on full clinical hold by the United States Food and Drug Administration (FDA). All trials including treatment involving pacritinib have been stopped, and the New Drug Application (NDA) to the FDA for pacritinib has been withdrawn.1
Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm that is chronic and progressive in nature. It involves the abnormal development and function of bone marrow cells that produce blood cells and leads to the formation of scar tissue in the bone marrow. When the bone marrow becomes scarred it can’t make enough blood cells and this can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with myelofibrosis, the condition progresses to acute myeloid leukemia. Myelofibrosis is rare and affects ~18,000 people in the U. S. Although it can occur at any age it most commonly occurs in individuals over 65.
When myelofibrosis develops on its own (and not as the result of another bone marrow disease), it’s called primary myelofibrosis. Myelofibrosis can also result from a worsening of other bone marrow diseases, such as polycythemia vera and essential thrombocythemia.
Pacritinib is a JAK2/FLT3 inhibitor that had recently entered the final phase (phase III) of clinical trials for the treatment of myelofibrosis. Pacritinib had already been granted fast-track designation by the FDA for the treatment of intermediate and high-risk myelofibrosis. Results from an earlier clinical trial evaluating pacritinib had demonstrated promising results when compared to best standard therapies in myelofibrosis.2
However, side effects that resulted in patient deaths related to bleeding in the brain (intracranial hemorrhage), cardiac arrest and heart failure in the current PERSIST-2 trial resulted in the FDA placing a full clinical hold on pacritinib, including the immediate discontinuation of treatment with pacritinib for all patients.
According to a press release by CTI BioPharma regarding the clinical hold, the FDA has recommended “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 protocols. In addition, the FDA recommended that the company request a meeting prior to submitting a response to full clinical hold.”
In an earlier clinical trial (the PERSIST-1trial), pacritinib demonstrated significant improvements in spleen volume and overall symptoms among patients with myelofibrosis, compared to best standard therapy (excluding Jakafi). 2
Until the FDA provides further notification, pacritinib remains on full clinical hold. For updated information, please visit www.ctibiopharma.com.
- CTI BioPharma Provides Update On Clinical Hold Of Investigational Agent Pacritinib And New Drug Application In U.S. Available at: http://investors.ctibiopharma.com/phoenix.zhtml?c=92775&p=RssLanding&cat=news&id=2137027. Accessed April 20, 2016.
- Mesa R, Egyed M, Szoke A, et al. Results of the PERSIST-1 phase III study of pacritiib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polychythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF). Presented at the 2015 ASCO annual meeting: May 29-June 2, 2015. Chicago, IL. Abstract LBA7006.
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