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|Long-Term Follow Up Data For Pacritinib Presented At 2016 ASCO Annual Meeting|
"From the time a patient is diagnosed with myelofibrosis, the incidence of disease-related thrombocytopenia increases with time," stated
Dr. Harrison added, "It is encouraging to see that patients with baseline thrombocytopenia who were treated with pacritinib, had stable mean platelet counts and hemoglobin levels through the end of treatment, and that some patients with very low platelets increased their platelet counts while receiving pacritinib treatment. In this intermediate- to high-risk patient group, pacritinib was generally well tolerated."
Myelofibrosis is a rare, but serious and life-threatening chronic leukemia that disrupts the normal production of blood cells and results in scarring of the bone marrow, limiting the ability to produce new blood cells and prompting the spleen and other organs to take over this function. The disease often leads to an enlarged spleen and lower than normal counts of blood cells – including red blood cells and platelets, which are essential for blood clotting. Frequent causes of death among patients with myelofibrosis include leukemic transformation (31 percent), disease progression (18 percent), and thrombosis and cardiovascular complications (13 percent) 1.
Below are highlights presented at the 52nd Annual Meeting of the
Highlights of Data Presented
In this poster, an update on efficacy and safety of the PERSIST-1 clinical trial up to Week 72 is provided for all patients in the study (pacritinib n=220; BAT n=107), regardless of platelet count. Ninety patients (84 percent) randomized to BAT crossed over to receive pacritinib at a median of 27.2 weeks.
Responses to pacritinib were durable and rates of 35 percent or greater spleen volume reduction (SVR) were maintained from Weeks 24 to 72 (25 percent vs. 24 percent). Patients who crossed over to receive pacritinib achieved similar responses to those receiving initial treatment with pacritinib. Overall survival, although not a primary or secondary endpoint of the trial, did not show a statistically significant difference between the pacritinib and BAT arms. This was primarily due to an imbalance between the two arms, with higher risk patients in the pacritinib arm vs. BAT. The result was potentially confounded by a high percentage of patients who crossed over at Week 24 to receive pacritinib therapy. Pacritinib-treated patients who achieved SVR greater or equal to 20 percent had statistically significant longer overall survival vs. patients who did not achieve SVR at this level.
The most frequently occurring adverse events with pacritinib were gastrointestinal events and the incidence decreased over time. Incidence of grade 3/4 treatment-emergent diarrhea with initial pacritinib treatment was highest in Weeks 1-8 (3 percent) and decreased in Weeks 8-16 (1.4 percent), Weeks 16-24 (1.5 percent) and in the final period analyzed, Weeks 64-72 (0.9 percent). Up to 24 weeks, prior to the majority of patients in the BAT arm crossing over, there was no statistically significant difference in the incidence of cardiac and bleeding adverse events between the pacritinib and BAT arms; following crossover to pacritinib, BAT patients had a similar rate of all grades of adverse events. The incidence of all grade cardiac AEs was similar between pacritinib and BAT arms between Weeks 1 and 24; incidence of cardiac AEs was greater for pacritinib between Weeks 24 and 72 vs. BAT, but was low overall (5 percent or less at any time). Among all patients, incidence of grade 3/4 bleeding events was 3 percent or less during any 8-week time interval.
This analysis examines outcomes up to 72 weeks among patients in the PERSIST-1 trial with baseline platelets less than 100,000 per microliter treated with pacritinib vs. BAT (pacritinib, n=72; BAT, n=34). For patients receiving pacritinib, a median duration of spleen volume reduction (SVR) of 35 percent or greater was 48 weeks for patients with baseline platelets less than 50,000 per microliter and 57 weeks for patients with baseline platelets less than 100,000 per microliter. For BAT-treated patients who crossed over to receive pacritinib before or after Week 24, duration of SVR was 73 weeks for patients with baseline platelets less than 50,000 per microliter and 46 weeks for patients with baseline platelets less than 100,000 per microliter. At Week 36, 46 percent (6/13) of evaluable pacritinib-treated patients with baseline platelets less than 50,000 per microliter and 48 percent (12/28) of evaluable pacritinib-treated patients with baseline platelets less than 100,000 per microliter achieved 50 percent or greater reduction in Total Symptom Score (TSS). This is an increase from 32 percent and 42 percent, respectively, at Week 24.
Patients treated with pacritinib had stable mean platelet counts and hemoglobin levels through Week 72 and increased platelet counts in patients with platelets less than 50,000 per microliter. At 24 weeks, bleeding events occurred at a similar rate in pacritinib-and BAT-treated patients; following crossover to pacritinib, BAT patients had a similar rate of events. Among patients with baseline thrombocytopenia treated with pacritinib, mean hemoglobin levels remained stable through Week 72. Due to BAT crossover to pacritinib at Week 24, there were no evaluable patients with baseline thrombocytopenia in the BAT arm beyond Week 36. These data suggest pacritinib treatment led to durable reductions in spleen volume and symptom burden.
In this poster, pacritinib-treated patients demonstrated clinically meaningful reductions in spleen volume independent of
Twenty-two percent (12/54) of RBC-TD patients treated with pacritinib either from study start or after crossover achieved RBC-TI during the course of the study. During the course of the study, 25 percent (9/36) of RBC-TD patients treated with pacritinib at the start of the study achieved RBC-TI vs. 0 percent (0/16) patients treated with BAT (p=0.043). Seventeen percent (3/18 patients) of RBC-TD patients at the time of crossover achieved RBC-TI during the crossover period. Pacritinib treatment was associated with improved patient outcomes for those with baseline RBC-TD.
Patient Reported Outcomes (PRO) data at 24 weeks was previously reported and the poster presented today provided an update at Week 48. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a PRO assessment tool designed to measure myelofibrosis-related symptom burden resulting in a TSS based on how the patient feels or functions in relation to six common symptoms. The proportion of patients achieving a TSS reduction of 50 percent or greater improved from Weeks 24 to 48 and was greater than observed with BAT showing that reduction in symptoms continued to increase over time. In patients who crossed over from BAT to pacritinib, reductions in TSS improved from Week 24 to Week 36. Mean percentage reductions in common symptoms measured in both MPN-SAF versions at Week 48 were greater than those observed at Week 24 among patients treated with pacritinib.
PERSIST-1 is a randomized (2:1), controlled Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT – which included a broad range of currently utilized treatments – in 327 patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis), regardless of the patients' platelet counts. As previously reported, the trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan) in the intent-to-treat population (ITT). These results included patients with severe or life-threatening thrombocytopenia. At study entry, 62 percent of patients had primary myelofibrosis; 46 percent of patients were thrombocytopenic; 32 percent of patients had baseline platelet counts less than 100,000 per microliter; and 16 percent of patients had platelet counts less than 50,000 per microliter; normal platelet counts range from 150,000 to 450,000 per microliter. The design of PERSIST-1 allowed for patients on the BAT arm to crossover and receive treatment with pacritinib if their disease progresses or after they achieve the 24-week measurement endpoint. Although crossover design of clinical trials may confound evaluation of survival, which is a tertiary endpoint of PERSIST-1, such designs are frequently used in cancer studies. The median duration of treatment was 16.2 months in patients treated with pacritinib, compared to 5.9 months in patients treated with BAT. The majority of patients (84 percent) on the BAT arm eventually crossed over to receive pacritinib therapy.
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In
About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera and essential thrombocythemia.2
Myelofibrosis is a serious and life-threatening 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. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue, and pain.
The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S., of which myelofibrosis accounts for approximately 18,000 patients.3 In
About CTI BioPharma
This press release includes forward-looking statements, which are 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 the issuers' securities. Such statements include, but are not limited to, expectations with respect to the potential therapeutic utility of pacritinib, including pacritinib's potential to achieve treatment goals across patients with myelofibrosis, regardless of baseline characteristics, such as starting platelet count and in particular, its potential to reduce spleen volume and symptom burden and improve HRQoL, and expectations for the future availability of top-line results from the PERSIST-2 Phase 3 trial of pacritinib. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. In particular, this release addresses select clinical trial data and results, and should be evaluated together with information regarding primary and secondary endpoints, safety and additional data once such data has been more fully analyzed and is made publicly available. The statements are based on assumptions about many important factors and information currently available to us to the extent we have thus far had an opportunity to fully and carefully evaluate such information in light of all surrounding facts, circumstances, recommendations and analyses. A number of results and uncertainties could cause actual results to differ materially from those in the forward-looking statements, including: satisfaction of regulatory and other requirements; that trial results observed to date may differ from future results or that different conclusions or considerations may qualify such results once existing data has been more fully evaluated;actions of regulatory bodies and other governmental authorities; other clinical trial results; changes in laws and regulations; product quality, product efficacy, study protocol, data integrity or patient safety issues; product development risks; and other risks identified in each of the issuer's most recent filings on Forms 10-K and 10-Q and other
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