Rare Disease Report

Phase 3 Myelofibrosis Trial With Pacritinib Meets Primary Endpoint

MARCH 09, 2015
James Radke

Pacritinib is one step closer to getting approved for the treatment of patients with myelofibrosis. 

CTI BioPharma and Baxter International announced their phase 3 PERSIST-1 trial met its primary endpoint [patients achieving a 35% or greater reduction in spleen volume when compared with physician-specified best available therapy (BAT)].

Pacritinib is a next generation oral JAK2/FLT3 multikinase inhibitor that was given fast track designation in December 2014. The PERSIST-2 trial is one of two trials that plan to be used as part of the New Drug Application to be submitted to the US Food and Drug Administration (FDA).

PERSIST-1 is a randomized (2:1), open-label, multinational Phase 3 clinical trial comparing the efficacy and safety of pacritinib with that of BAT, other than JAK inhibitors, in 327 patients with primary and secondary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), without exclusion for low platelet counts. The primary endpoint assessed the proportion of patients achieving a 35% or greater reduction in spleen volume from baseline to Week 24 as measured by MRI or CT, when compared with BAT, excluding treatment with JAK2 inhibitors. After the completion of 24 weeks of treatment or disease progression, crossover from the BAT arm to pacritinib was allowed.

Analysis of the data showed that patients receiving pacritinib had a clinically and statistically significant difference in spleen volume reduction to those receiving BAT (P = .0003). The trial also demonstrated a significant difference among patients with platelet counts of less than 100,000 per microliter and less than 50,000 per microliter.

The most common treatment emergent adverse events were diarrhea, nausea and vomiting, the incidence of grade 3 events was lower than observed in Phase 2 trials. No grade 4 gastrointestinal adverse events were reported. Three patients discontinued therapy and 9 patients required dose reduction for diarrhea.

One of the principal investigators of the study, Claire Harrison, MD, Consultant Hematologist, Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital, London, said:

"Despite the introduction of JAK2 inhibitors as effective therapies for patients with myelofibrosis, there remains a treatment gap for patients with disease-related or treatment emergent thrombocytopenia. The currently approved drug may require dose titration to less effective doses in this patient population, thus limiting our ability to effectively treat them. Results from the PERSIST-1 randomized trial demonstrate that pacritinib could address this unmet medical need."

"It is encouraging to see that patients were able to receive therapeutic doses of pacritinib over a long period of time irrespective of their baseline platelet or red blood cell count while having therapeutic benefit in reduction in spleen volume and disease-related symptoms and improvement in transfusion dependency."

James A. Bianco, M.D., CTI BioPharma's President and CEO added:
"PERSIST-1 is the first randomized Phase 3 trial investigating the potential benefit of a JAK2 inhibitor across a patient population with myelofibrosis that is representative of patients that healthcare providers see and treat in clinical practice."

Pacritinib is an oral multikinase inhibitor with dual activity against JAK2 and FLT3. The kinase profile of pacritinib suggests its potential therapeutic utility for many types of rare cancers [acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL)] but at the present time, it only has orphan drug designation for myelofibrosis.

Myelofibrosis is a one of three main types of myeloproliferative neoplasms.  The other two types are polycethemia vera, essential thrombocytopenia. Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function.

There are approximately 18,000 people in the United States with myelofibrosis. U.S. Median survival for myelofibrosis patients is approximately 6 years.  Currently, Jakafi (ruxolitinib) is the only approved orphan drug for these patients.


CTI BioPharma And Baxter Announce Positive Top-Line Results From Phase 3 Persist-1 Trial Of Pacritinib For Patients With Myelofibrosis []press release]. Seattle WA and Deerfield Ill; CTI Biopharma and Baxter International; March 9, 2015. http://www.prnewswire.com/news-releases/cti-biopharma-and-baxter-announce-positive-top-line-results-from-phase-3-persist-1-trial-of-pacritinib-for-patients-with-myelofibrosis-300047194.html . Accessed March 9, 2015.

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