SEATTLE, Jan. 5, 2017 /PRNewswire/ -- CTI BioPharma
Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) today announced that
the full clinical hold (February
2016) implemented by the U.S. Food and Drug Administration
(FDA) on all clinical trials conducted under the Investigational
New Drug (IND) application for pacritinib has now been removed. The
Company's complete response submission included, among other items,
final Clinical Study Reports for both PERSIST-1 and 2 trials and a
dose-exploration clinical trial protocol that the FDA
requested. The new trial, PAC203 plans to enroll up to
approximately 105 patients with primary myelofibrosis who have
failed prior ruxolitinib therapy to evaluate the safety and the
dose response relationship for efficacy (spleen volume reduction at
24 weeks) of three dose regimens: 100 mg once-daily, 100 mg
twice-daily (BID) and 200 mg BID. The 200 mg BID dose regimen was
used in PERSIST-2. The Company expects to start the trial in the
second quarter of 2017.
"We are pleased to resolve the full clinical hold through
working diligently with the FDA to provide a comprehensive response
to their requests," said Richard
Love, Interim President and CEO of CTI BioPharma. "We look
forward to discussing with the FDA the future development of
pacritinib. We believe pacritinib can ultimately
address the unmet need of patients with myelofibrosis who are
ineligible to receive or are not benefitting from the approved
JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited
treatment options."
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 investigational new drug (IND) for
pacritinib were subject to a full clinical hold issued by the FDA
in February 2016. 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, 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. The trial
met its primary endpoint of spleen volume reduction (35 percent or
greater from baseline to Week 24 by MRI/CT scan).
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). Patients were randomized to
receive 200 mg pacritinib twice daily (BID), 400 mg pacritinib once
daily (QD) or BAT. Results of the trial were presented at the
American Society of Hematology Annual meeting in Dececember 2016. The trial met one of its
co-primary endpoints, that of spleen volume reduction (35 percent
or greater from baseline to Week 24 by MRI/CT scan). The co-primary
endpoint of reduction of Total Symptom Score (TSS) was not achieved
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. 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 BID showed a higher
percent of SVR and TSS responses compared to BAT; whereas,
pacritinib given QD showed only a higher percent SVR responses
compared to BAT. There was no significant difference in overall
survival (OS) across treatment arms, censored at the time of
clinical hold. 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.
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 the timing and planned enrollment of PAC203 and
our ability to be able to interpret clinical trial data and
results 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
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SOURCE CTI BioPharma Corp.