Cell Therapeutics, Inc. (CTI) has started phase III clinical trial, known as PERSIST-2, which will evaluate pacritinib, a novel, investigational JAK2/FLT3 inhibitor, in patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter (uL). The trial is expected to enroll up to 300 patients in North America, Europe, Australia and New Zealand within 12 to 14 months.
In October 2013, CTI reached agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the PERSIST-2 trial, which is a written agreement between CTI and the FDA regarding the planned design, endpoints and statistical analysis approach of the trial to be used in support of a potential New Drug Application, or NDA, submission. PERSIST-2 is the second of two planned phase III trials in the pacritinib development program for myelofibrosis.
"JAK2 inhibitors have revolutionized the treatment of myelofibrosis by providing patients with an effective way to manage their disease," said Srdan Verstovsek, MD, PhD, principal investigator of PERSIST-2 and professor, Leukaemia Department, Division of Cancer Medicine, chief, Section for Myeloproliferative Neoplasms, Leukaemia Department, and director, Clinical Research Centre for MPNs, at The University of Texas MD Anderson Cancer Centre. "However, I believe there remains a significant unmet medical need for new therapies, particularly for patients who present with or develop thrombocytopenia while on treatment. We are pleased to have the PERSIST-2 trial underway to evaluate the ability of pacritinib to address this issue."
PERSIST-2 is a randomized, open-label, multi-centre clinical trial evaluating pacritinib in patients with myelofibrosis (a myeloproliferative neoplasm and chronic bone marrow disorder) whose platelet counts are less than or equal to 100,000/uL. The trial will evaluate pacritinib as compared to best available therapy, including approved JAK2 inhibitors that are dosed according to the product label for myelofibrosis patients with thrombocytopenia. Patients will be randomized (1:1:1) to receive 200 mg pacritinib twice daily (BID), 400 mg pacritinib once daily (QD) or best available therapy. Under the SPA, the agreed upon co-primary endpoints are the percentage of patients achieving a 35 per cent or greater reduction in spleen volume measured by MRI or CT scan from baseline to 24 weeks of treatment and the percentage of patients achieving a Total Symptom Score (TSS) reduction of 50 per cent or greater using six key symptoms as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to 24 weeks.
"With the initiation of the PERSIST-2 trial, we believe that the registration program for pacritinib is on track for a potential NDA submission in the latter part of 2015," said James A Bianco, MD, president and CEO of CTI. "We have seen meaningful clinical benefits and good tolerability with pacritinib in myelofibrosis patients in phase II trials without apparent drug-related thrombocytopenia or anemia. As such, we have had strong interest in site participation for this trial and will work diligently to activate these sites over the next several months."
Based on pacritinib's efficacy and tolerability profile demonstrated to date, CTI is pursuing a broad approach to advancing this therapy for myelofibrosis patients by conducting two phase III clinical trials: one in a broad set of patients without limitations on blood platelet counts, the ongoing PERSIST-1 trial, and the other in patients with low platelet counts, the PERSIST-2 trial, as described above.
In January 2013, CTI initiated PERSIST-1, which is a 270 patient randomized, open-label, multicentre phase III trial comparing the efficacy and safety of pacritinib with that of best available therapy in patients with myelofibrosis. Best available therapy includes any physician-selected treatment other than JAK inhibitors and there is no exclusion by patient platelet count. The trial is currently enrolling patients at clinical sites in Europe, Australia, Russia and the United States.
Pacritinib is an oral tyrosine kinase inhibitor with dual activity against JAK2 and 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. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors.
In November 2013, CTI and Baxter International, Inc. (Baxter) entered into a worldwide license agreement to develop and commercialize pacritinib in which CTI and Baxter will jointly commercialize pacritinib in the United States and Baxter has exclusive commercialization rights for all indications outside the United States.
CTI is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable.