Integrated Safety and Efficacy Analysis of Phase 2 Clinical Trials of Pacritinib in Patients with Myelofibrosis and Low Platelet Counts Presented at ASH Annual Meeting
– Demonstrated clinically meaningful activity regardless of baseline platelet counts –
SEATTLE, Dec. 9, 2013 /PRNewswire/ — Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced results from an integrated analysis of data from two completed Phase 2 trials of investigational agent pacritinib, a novel, selective, oral JAK2/FLT3 inhibitor, demonstrating the efficacy and safety profile in patients with myelofibrosis (MF) whose baseline platelet counts are <=100,000/uL (low platelets) was comparable to that of patients with baseline platelet counts of >100,000/uL. The Phase 2 data demonstrated clinically meaningful spleen size and patient-reported symptom score reduction in MF patients with low platelets that were treated with pacritinib. Duration of exposure and average dose intensity were also unaffected by starting platelet counts. There were no significant differences observed in efficacy or safety parameters among patients with low platelet counts when compared to patients with higher platelet counts (>100,000/uL), including no clinically significant treatment-emergent anemia or thrombocytopenia. The analysis supports the planned second Phase 3 trial expected to start this month, known as PERSIST-2, which will evaluate pacritinib in patients with MF with low platelet counts compared to best available therapy, including the approved JAK2 inhibitor ruxolitinib at recommended doses for patients with low platelet counts. The results were presented today by Rami S. Komrokji, M.D., Clinical Director of the Malignant Hematology Department at the Moffitt Cancer Center and Research Institute, Tampa, Fla., during an oral presentation at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition held December 7-10, 2013 in New Orleans, La.
“The introduction of JAK2 inhibitors has had an important impact on the treatment of patients with myelofibrosis,” said Dr. Komrokji. “The integrated analysis of Phase 2 clinical trial data shows that pacritinib could potentially address an unmet need, particularly for patients with thrombocytopenia and anemia, a serious consequence of the disease itself, or certain therapies where myelosuppression is a limiting side effect for other JAK2 inhibitors. These results demonstrate the importance of continuing to evaluate JAK2 inhibitors in myelofibrosis, and their study should remain a high priority for the research community.”
Abstract #395: Pacritinib, a Dual JAK2/FLT3 Inhibitor: An Integrated Efficacy and Safety Analysis of Phase II Trial Data in Patients with Primary and Secondary Myelofibrosis (MF) and Platelet Counts <=100,000 uL
Integrated Phase 2 Trial Analysis Results
In this integrated analysis of two completed international Phase 2 trials of pacritinib, a total of 65 patients with MF were treated with 400 mg orally, once daily. Of these, 28 patients had baseline platelet counts of <=100,000/uL (median: 59,000/uL, range: 15,000/uL-97,000/uL) and 37 had baseline platelet counts >100,000/uL (median: 227,000/uL, range: 104,000-859,000/uL). The objective of the analysis was to evaluate the safety and efficacy of pacritinib in patients with MF with baseline platelet counts of <=100,000/uL or >100,000/uL. During these Phase 2 trials, spleen response was assessed by physical exam (PE) and MRI, and patient-reported outcomes used the Myelofibrosis Symptom Assessment Form (MF-SAF). Duration of exposure and daily dose were unaffected by baseline platelet counts.
Table 1- Spleen Response by MRI and PE
Endpoint Time Period Baseline Platelets Baseline Platelets All <=100,000/uL >100,000/uL (n=65) (n=28) (n=37) --- ----- ----- >=50% reduction in spleen volume by PE Up to 24 weeks 12/28 (43%) 14/34 (41%) 26/62(42%) --------- -------------- ----------- ----------- ---------- Up to last visit on treatment 13/28 (46%) 14/35 (40%) 27/63 (43%) -------------------- ----------- ----------- ----------- >=35% reduction in spleen size by MRI Up to 24 weeks 7/23 (30%) 6/26 (23%) 13/49 (27%) --------- -------------- ---------- ---------- ----------- Up to last visit on treatment 10/23 (44%) 8/26 (31%) 18/49 (37%) -------------------- ----------- ---------- -----------
Table 2 – >=50% Reduction in Patient-Reported Symptom Score*
Time Period Baseline Platelets Baseline Platelets All <=100,000/uL >100,000/uL (n=65) (n=28) (n=37) --- ----- ----- Up to 24 weeks 11/28 (39%) 16/34 (47%) 27/62 (44%) ------ ----------- ----------- ----------- Up to last visit on 13/28 (46%) 17/34 (50%) 30/62 (48%) treatment ---------
*The symptom score is the sum of the individual scores for worst fatigue, early satiety, abdominal pain or discomfort, night sweats, itching and bone pain reported on the MF-SAF.
This integrated safety analysis of all 65 patients showed the most common non-hematologic adverse events (occurring in 15 percent or more of patients overall) were gastrointestinal, predominantly diarrhea, and most were grade 1 or 2, regardless of baseline platelet counts. Of note, there were no thrombocytopenia-associated adverse events occurring at this frequency in either group. Per the protocols, anti-diarrheal prophylaxis was not used routinely in these early studies; time to onset of diarrhea was <=30 days, but rarely caused drug discontinuation (2 percent).
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 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.
As part of the new collaboration with Baxter, CTI is pursuing a broad approach to advancing pacritinib for patients with myelofibrosis by conducting two Phase 3 clinical trials: one in a broad set of patients without limitations on blood platelet counts, the PERSIST-1 trial; and the other will be in patients with low platelet counts, the PERSIST-2 trial, which is expected to begin in December 2013. In October 2013, CTI reached agreement with the U.S. Food and Drug Administration on a Special Protocol Assessment, or SPA, for the PERSIST-2 pivotal trial. A SPA is a written agreement between CTI and the FDA regarding the design, endpoints and planned statistical analysis approach of the trial to be used in support of a potential New Drug Application, or NDA, submission.
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.
About Cell Therapeutics, Inc.
CTI (NASDAQ and MTA: CTIC) is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable. CTI is headquartered in Seattle, WA. For additional information and to sign up for email alerts and get RSS feeds, please visit www.CellTherapeutics.com.
This press release includes forward-looking statements within the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements are subject to a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results and the trading price of CTI’s securities. Such statements include, but are not limited to, statements regarding CTI’s expectations with respect to the development of CTI and its product and product candidate portfolio, any current or potential collaborations or partnerships, the expected commencement of the PERSIST-2 clinical trial in the fourth quarter of 2013 and the expected efficacy and potential benefits of pacritinib (including that 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). Risks that contribute to the uncertain nature of the forward-looking statements include, among others, risks associated with the biopharmaceutical industry in general and with CTI and its product and product candidate portfolio in particular including, among others, risks associated with the following: that CTI cannot predict or guarantee the pace or geography of enrollment of its clinical trials, that CTI cannot predict or guarantee the outcome of preclinical and clinical studies, that the second Phase 3 clinical trial of pacritinib will not occur as planned, that CTI may not obtain favorable determinations by other regulatory, patent and administrative governmental authorities, that CTI may experience delays in the commencement of preclinical and clinical studies, risks related to the costs of developing pacritinib and CTI’s other product candidates, and other risks, including, without limitation, competitive factors, technological developments, that CTI’s operating expenses continue to exceed its net revenues, that CTI may not be able to sustain its current cost controls or further reduce its operating expenses, that CTI may not achieve previously announced goals and objectives as or when projected, that CTI’s average net operating burn rate may increase, that CTI will continue to need to raise capital to fund its operating expenses, but may not be able to raise sufficient amounts to fund its continued operation as well as other risks listed or described from time to time in CTI’s most recent filings with the Securities and Exchange Commission on Forms 10-K, 10-Q and 8-K. Except as required by law, CTI does not intend to update any of the statements in this press release upon further developments.
SOURCE Cell Therapeutics, Inc.