SEATTLE, Aug. 29, 2016 /PRNewswire/ -- CTI BioPharma
Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) today announced
top-line results from PERSIST-2, a randomized, controlled Phase 3
clinical trial comparing pacritinib, an investigational oral
multikinase inhibitor, with physician-specified best available
therapy (BAT), including ruxolitinib, for the treatment of patients
with myelofibrosis whose platelet counts are less than 100,000 per
microliter -- a patient population with high-risk advanced disease.
Three hundred eleven (311) patients were enrolled in the study,
which formed the basis for the safety analysis. Two hundred
twenty-one (221) patients who had a chance to reach Week 24 (the
primary analysis time point) at the time the clinical hold was
imposed and constituted the intent-to-treat (ITT) analysis
population utilized for the evaluation of efficacy. Preliminary
results demonstrated that the PERSIST-2 trial met one of the
co-primary endpoints showing a statistically significant response
rate in spleen volume reduction (SVR) in patients with
myelofibrosis treated with pacritinib compared to BAT, including
the approved JAK2 inhibitor ruxolitinib (p<0.01). Although the
PERSIST-2 trial did not meet the other co-primary endpoint of
greater than 50 percent reduction in Total Symptom Score (TSS), the
preliminary analysis approached marginal significance compared to
BAT (p=0.0791).
"Unlike patients with myelofibrosis who have normal baseline
platelet counts where median survival is reported at 88 months, we
recently reported from our institution's experience that patients
with severe thrombocytopenia (low platelets) had a median survival
of about 14 months," said Srdan (Serge) Verstovsek, M.D., Ph.D.,
Director, Clinical Research Center for MPNs at the University of Texas MD Anderson Cancer Center and
principal investigator for the PERSIST-2 Phase 3 clinical trial of
pacritinib. "These patients represent up to 30 percent of all
myelofibrosis patients and an unmet medical need. Data from the
PERSIST-2 prospective randomized, controlled trial is encouraging
because we need an effective therapy to treat the most challenging
patients with low platelet counts we see in our practice."
The co-primary endpoints of the trial were the proportion of
patients achieving a 35 percent or greater reduction in spleen
volume from baseline to Week 24 as measured by magnetic resonance
imaging (MRI) or computerized tomography (CT) and the proportion of
patients achieving a Total Symptom Score (TSS) reduction of 50
percent or greater using MPN-SAF TSS 2.0 diary from baseline to
Week 24.
The most common treatment emergent adverse events for pacritinib
were generally manageable diarrhea, nausea and vomiting. The
incidence of cardiac and bleeding adverse events (all grades and
grade 3-4 including deaths) were similar across the arms. Overall
mortality rates were comparable between arms. Additional data from
ongoing analyses along with top-line results from PERSIST-2 will be
submitted for presentation at an upcoming scientific meeting.
Myelofibrosis is associated with significantly reduced quality
of life and shortened survival. Spleen enlargement (splenomegaly)
is a common and debilitating symptom of myelofibrosis. As the
disease progresses, the body slows production of important blood
cells and within one year of diagnosis the incidence of
disease-related thrombocytopenia (very low blood platelet counts),
severe anemia and red blood cell transfusion requirements increase
significantly.
"Having analyzed data from two Phase 3 trials with the only
JAK inhibitor to be studied in severely thrombocytopenic patients,
including patients on JAK2 therapy or those who failed prior JAK2,
we are encouraged by pacritinib's clinical profile in this
difficult-to-treat group of patients with myelofibrosis," said
James A. Bianco, M.D.,
President and Chief Executive Officer, CTI BioPharma. "We are
grateful for the support and commitment of the investigators, our
steering committee and, most importantly, all the patients who
participated in PERSIST-2."
About PERSIST-2
PERSIST-2 was a randomized (1:1:1), controlled, open-label,
multinational Phase 3 clinical trial evaluating pacritinib compared
to best available therapy (BAT), including the approved JAK1/JAK2
inhibitor ruxolitinib, for patients with myelofibrosis whose
platelet counts were less than or equal to 100,000 per microliter
(≤100,000/μL). Three hundred eleven (311) patients were randomized
to receive 200 mg pacritinib twice daily (BID), 400 mg pacritinib
once daily (QD) or BAT. Clinical studies for pacritinib are
currently subject to a full clinical hold issued by the U.S. Food
and Drug Administration (FDA) in February
2016. The study was originally designed to enroll, and the
Special Protocol Assessment (SPA) requires enrollment of 300
patients to evaluate the study objectives. Two hundred twenty-one
(221) patients were enrolled at least 24 weeks prior to the full
clinical hold and thus were potentially evaluable for efficacy.
These patients were the population used to evaluate the study
efficacy endpoints. The co-primary endpoints, originally agreed
upon under the SPA, were the percentage of patients achieving a 35
percent or greater reduction in spleen volume measured by MRI or CT
scan from baseline to Week 24 of treatment and the percentage of
patients achieving a Total Symptom Score (TSS) reduction of 50
percent or greater using seven key symptoms as measured by the
modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF
TSS 2.0) diary from baseline to Week 24. The primary objective of
the study was to compare pooled pacritinib arms vs BAT. As a result
of the full clinical hold on pacritinib, the SPA agreement is no
longer in effect for PERSIST-2 and CTI BioPharma is no longer
entitled to the benefit of the SPA.
About the Phase 3 Development Program of Pacritinib
Pacritinib was evaluated in two Phase 3 clinical trials, known
as the PERSIST program, for patients with myelofibrosis, with one
trial in a broad set of patients without limitations on platelet
counts, the PERSIST-1 trial; and the other in patients with low
platelet counts, the PERSIST-2 trial. In August 2014, pacritinib was granted Fast Track
designation by the FDA for the treatment of intermediate and high
risk myelofibrosis including, but not limited to, patients with
disease-related thrombocytopenia (low platelet counts); patients
experiencing treatment-emergent thrombocytopenia on other JAK2
inhibitor therapy; or patients who are intolerant of, or whose
symptoms are not well controlled (sub-optimally managed) on other
JAK2 therapy.
Clinical studies under the CTI BioPharma investigational new
drug (IND) for pacritinib are currently subject to a full clinical
hold issued by the U.S. Food and Drug Administration in
February 2016.
PERSIST-1 was a randomized (2:1), controlled, open-label,
multinational Phase 3 trial evaluating the efficacy and safety of
pacritinib compared to BAT, excluding JAK2 inhibitors, 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. The study included patients with severe or
life-threatening thrombocytopenia. Patients were randomized to
receive 400 mg pacritinib once daily or BAT, excluding JAK2
inhibitors. 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).
About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with
specificity for JAK2, FLT3, IRAK1 and CSF1R. 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. In addition to
myelofibrosis, the kinase profile of pacritinib suggests its
potential therapeutic utility in conditions such as acute myeloid
leukemia, or AML, myelodysplastic syndrome, or MDS, chronic
myelomonocytic leukemia, or CMML, and chronic lymphocytic leukemia,
or CLL, due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.
CTI BioPharma and Shire are parties to a worldwide license
agreement to develop and commercialize pacritinib. CTI BioPharma
and Shire will jointly commercialize pacritinib in the U.S. while
Shire has exclusive commercialization rights for all indications
outside the U.S.
About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is one of three main types of myeloproliferative
neoplasms (MPN), which are a closely related group of progressive
blood cancers. The three main types of MPNs are primary
myelofibrosis (PMF), polycethemia vera (PV) and essential
thrombocythemia (ET).1
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.2 In Europe,
there is a wide variation of prevalence observed across data
sources. Myelofibrosis has a median age of 64 at the time of
diagnosis3 and is a progressive disease with
approximately 20 percent of patients eventually developing acute
myeloid leukemia (AML).4 The median survival for
high-risk myelofibrosis patients is less than 1.5 years, while the
median survival for patients with myelofibrosis overall is
approximately 6 years.4
About CTI BioPharma
CTI BioPharma Corp. is a biopharmaceutical company focused on
the acquisition, development and commercialization of novel
targeted therapies covering a spectrum of blood-related cancers
that offer a unique benefit to patients and healthcare providers.
CTI BioPharma has a commercial presence in Europe with respect to PIXUVRI® and
a late-stage development pipeline, including pacritinib for the
treatment of patients with myelofibrosis. CTI BioPharma is
headquartered in Seattle,
Washington, with offices in London and Milan under the name CTI Life Sciences
Limited. For additional information and to sign up for email alerts
and get RSS feeds, please visit www.ctibiopharma.com.
Forward-Looking Statements
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 our ability to be able to interpret clinical trial data
and results despite not satisfying the pre-specified minimum
evaluable patient goal and 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. 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 press release addresses select preliminary
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. In addition, meaningful interpretation
of PERSIST-2 may not be possible because the pre-specified minimum
evaluable patient goal was not met. 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 Securities and Exchange Commission filings.
Except as required by law, CTI Biopharma does not intend to update
any of the statements in this press release upon further
developments.
- MPN Research Foundation. Accessed August
2016. Available at www.mpnresearchfoundation.org.
- Based on Mesa R, ASH 2012 poster.
- Cervantes F, et al., New prognostic scoring system for primary
myelofibrosis based on a study of the International Working Group
for Myelofibrosis Research and Treatment. Blood. 2009;
113:2895-2901.
- Vannucchi, A. Management of Myelofibrosis. ASH Education Book.
2011; 1:222-230.
CTI BioPharma Contacts:
Monique Greer
+1 206-272-4343
mgreer@ctibiopharma.com
Ed Bell
+1 206-272-4345
ebell@ctibiopharma.com
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