SEATTLE, Dec. 6, 2016 /PRNewswire/ -- CTI BioPharma Corp.
(CTI BioPharma) (NASDAQ and MTA: CTIC) today announced data from
PERSIST-2, a randomized Phase 3 clinical trial comparing pacritinib
with physician-specified best available therapy (BAT), for the
treatment of high risk, thrombocytopenic myelofibrosis patients
(platelet counts less than 100,000 per microliter) in a
late-breaking oral session at the 58th American Society
of Hematology (ASH) Annual Meeting, December
3-6 in San Diego, CA.
Pacritinib is an investigational oral multikinase inhibitor. Data
presented at ASH (Abstract #LBA-5) show that in myelofibrosis
patients a statistically significant response rate in spleen volume
reduction (SVR) with pacritinib therapy was observed compared to
BAT that included use of the approved JAK1/JAK2 inhibitor
ruxolitinib (p=0.001). The co-primary endpoint of reduction of
Total Symptom Score (TSS) was not achieved (p=0.079) but trended
toward improvement in TSS. Irrespective of prior ruxolitinib
treatment, pacritinib therapy resulted in a statistically
significant higher proportion of patients with SVR than patients on
BAT.
"Patients with myelofibrosis who have low platelet counts are
often intolerant of ruxolitinib therapy and have no effective
treatment options," said John
Mascarenhas, M.D., Associate Professor, The Tisch Cancer
Institute at the Icahn School of Medicine at Mount Sinai and the
presenter of the results in an oral presentation at ASH. "Data from
PERSIST-2 suggest that pacritinib dosed on a twice-daily schedule
may prove to be effective therapy for thrombocytopenic
myelofibrosis patients with an adequate safety profile to fill
an important unmet clinical need."
PERSIST-2 Results Presented at ASH
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. At the time, the FDA noted interim overall survival
results from the PERSIST-2 showing a detrimental effect on survival
were consistent with the results from PERSIST-1. Two hundred
twenty-one (221) patients (74 pacritinib BID; 75 pacritinib QD; 72
BAT) were enrolled at least 24 weeks prior to the full clinical
hold and were potentially evaluable for the Week 24 efficacy
endpoint (ITT efficacy population). In the ITT efficacy population
at study entry, 46 percent (101/221) of patients had platelet
counts less than 50,000 per microliter (<50,000/μL), and 59
percent (130/221) were anemic (hemoglobin <10 g/dL). Normal
platelet counts range from 150,000 to 450,000 per microliter. The
percentage of patients in the ITT efficacy population who received
prior ruxolitinib was as follows: 41 percent (31/75) pacritinib QD;
42 percent (31/74) pacritinib BID; and 46 percent (33/72) BAT.
Safety analyses were based on all patients exposed to study
treatment of any duration.
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 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 versus BAT and the secondary objectives were to
compare pacritinib BID and QD arms individually to BAT. Study was
designed to evaluate the study objectives with sample size of 300.
At the time of clinical hold, study enrollment was completed with
311 patients randomized, but only 221 patients had the potential to
be evaluated for efficacy endpoints at Week 24.
As previously reported, the PERSIST-2 trial met one of the
co-primary endpoints showing a statistically significant response
rate in SVR in patients with myelofibrosis treated with pacritinib
combining the once- and twice-daily arms compared to BAT. Although
the PERSIST-2 trial did not meet the other co-primary endpoint of
greater than 50 percent reduction in TSS, the results approached
marginal significance compared to BAT. Although secondary
objectives could not be evaluated formally due to the study not
achieving one of the primary objectives, when the two pacritinib
dosing arms were evaluated separately versus BAT, pacritinib given
twice daily showed a higher percent of SVR and TSS responses
compared to BAT; whereas, pacritinib given once daily showed only a
higher percent SVR responses compared to BAT.
Spleen Volume
Reduction of ≥35%; Total Symptom Score Reduction of ≥50% at Week
24
|
|
|
Pacritinib
|
BAT
|
p-value*
|
Pooled BID and QD
– Primary objectives
|
SVR
|
18%
|
3%
|
0.001
|
TSS
|
25%
|
14%
|
0.079
|
|
BID – 200 mg twice
daily – Secondary objectives
|
SVR
|
22%
|
3%
|
0.001
|
TSS
|
32%
|
14%
|
0.011
|
|
QD – 400 mg once
daily – Secondary objectives
|
SVR
|
15%
|
3%
|
0.017
|
TSS
|
17%
|
14%
|
0.652
|
|
* p-value for the
secondary objectives were nominal p-values and used for
reference.
|
A total of 45 percent of the BAT patients randomized received
ruxolitinib at some point on the study.
There was no significant difference in overall survival (OS)
across treatment arms, censored at the time of clinical hold.
Hazard ratios (95% confidence intervals (CI)) were 0.68 (0.30-1.53)
for pacritinib BID versus BAT and 1.18 (0.57-2.44) for pacritinib
QD versus BAT. Overall mortality rates at that time were comparable
between arms: 9 percent BID versus 14 percent QD and 14 percent
BAT.
The most common treatment-emergent adverse events (AEs),
occurring in 20 percent or more of patients treated with pacritinib
within 24 weeks, of any grade, were gastrointestinal (generally
manageable diarrhea, nausea and vomiting) and hematologic (anemia
and thrombocytopenia) and were generally less frequent for BID
versus QD administration. The most common serious
treatment-emergent AEs (incidence of ≥5 percent reported in any
treatment arm irrespective of grade) were anemia, thrombocytopenia,
pneumonia and acute renal failure none of which exceeded 8 percent
individually in any arm.
"In this randomized Phase 3 clinical trial in
thrombocytopenic patients with advanced myelofibrosis that allowed
for prior therapy with a JAK inhibitor and allowed use of
ruxolitinib in the best available therapy arm," 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, "the data demonstrates
pacritinib's activity in this challenging patient population and
shows the potential for pacritinib to effectively retreat patients
following failure of anti-JAK2 treatment."
"CTI BioPharma would like to thank all the patients and
physicians that participated in the PERSIST-2 trial," said
Richard Love, Interim President and
CEO of CTI BioPharma. "We are committed to bringing pacritinib to
the many myelofibrosis patients in need of new therapies and will
continue to work with the regulatory agencies to move the process
forward."
Data will be presented today by John Mascarenhas, M.D., in
a late-breaking oral session at 8:30 a.m. PT and was selected
as part of the official ASH press program. The presentation will be
available at www.ctibiopharma.com following the conclusion of the
meeting.
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. At the time, the FDA
noted interim overall survival results from the PERSIST-2 showing a
detrimental effect on survival were consistent with the results
from PERSIST-1 and that deaths in PERSIST-2 in pacritinib-treated
patients include intracranial hemorrhage, cardiac failure and
cardiac arrest.
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.
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
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 Contact:
Ed Bell
+1 206-272-4345
ebell@ctibiopharma.com
Logo - http://photos.prnewswire.com/prnh/20140529/92480
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/persist-2-phase-3-study-of-pacritinib-versus-best-available-therapy-shows-encouraging-clinical-activity-in-high-risk-patients-with-advanced-myelofibrosis-in-late-breaking-session-at-ash-annual-meeting-300373387.html
SOURCE CTI BioPharma Corp.