Cell Therapeutics, Inc. (CTI), a biopharmaceutical company, has initiated clinical trial sites and began enrolling patients in a phase III clinical trial, known as PERSIST-1 or PAC325, for pacritinib, CTI's investigational JAK2 inhibitor, which is being evaluated for the treatment of patients with myelofibrosis. The randomized trial is expected to enroll 270 patients and will evaluate the safety and efficacy of pacritinib compared to best available therapy, excluding JAK inhibitors, in patients with myelofibrosis.

Pacritinib is a selective oral JAK2 inhibitor that demonstrated meaningful clinical benefits and good tolerability in myelofibrosis patients in phase II clinical trials, without apparent drug-related thrombocytopenia or anaemia.  Myelofibrosis patients will be enrolled in the PERSIST-1 trial without exclusion for low platelet counts.

Principal Investigators for the trial are Ruben A Mesa, MD, deputy director, Mayo Clinic Cancer Centre and Chair, Hematology and Medical Oncology, Mayo Clinic in Arizona, and Claire Harrison, MD, consultant haematologist, Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital, London, United Kingdom.

"Current treatment of myelofibrosis by targeting JAK2 inhibition has been shown to be effective in managing the debilitating symptoms that are associated with this disease, although thrombocytopenia and anemia continue to be a challenge in managing this disease," said Steven E Benner, MD, chief medical officer of CTI.  "Data from earlier studies of pacritinib showed a clinically meaningful improvement in symptoms without suppression of platelets or red blood cells. We believe that pacritinib has the potential to offer an effective and well-tolerated treatment option for myelofibrosis patients, and are pleased to be initiating the phase III PERSIST-1 clinical trial."

Myelofibrosis is classified as a myeloproliferative neoplasm and is a chronic bone marrow disorder. Myelofibrosis is caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response, scarring the bone marrow and limiting its ability to produce red blood cells prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue and pain. It is estimated that the prevalence of myelofibrosis is approximately 30,000 in the United States.

PERSIST-1 is a multicentre, randomized, controlled phase III trial comparing the efficacy and safety of pacritinib with that of best available therapy in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. A total of 270 eligible patients will be randomized 2:1 to receive either pacritinib 400 mg taken orally, once daily or the best available therapy.  Best available therapy includes any physician-selected treatment with the exclusion of JAK inhibitors.  There will be no exclusion by patient platelet count. The primary endpoint will be the percentage of patients achieving a = 35% reduction in spleen volume measured by MRI or CT at 24 weeks of treatment. The trial is expected to enroll patients at clinical sites in Europe, Australia and the United States.

PERSIST-1 is the first of two planned phase III clinical trials in patients with myelofibrosis. The second phase III clinical trial is planned to evaluate pacritinib compared to best available therapy, including JAK inhibitors, in patients with myelofibrosis whose platelet counts are <100,000 / µL.

Pacritinib is an oral, once-a-day, tyrosine kinase inhibitor (TKI) with dual activity against JAK2 and FLT3. The JAK family of enzymes are 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, leukaemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anaemia than has been seen in currently approved and in-development JAK inhibitors. Pactrinib has demonstrated encouraging results in phase I and II studies for patients with myelofibrosis. Pacritinib has orphan drug designation in the US and Europe.

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