EWING, N.J., June 14, 2016 /PRNewswire/ -- Celator
Pharmaceuticals, Inc. (Nasdaq: CPXX) today announced positive
response rate results in AML patients with FLT3 (FMS-like tyrosine
kinase-3) mutation were presented at the European Hematology
Association (EHA) 21st Annual Congress. The results are
from the Company's Phase 3 trial of VYXEOS™ (cytarabine:
daunorubicin) Liposome for Injection (also known as CPX-351) in
patients with high-risk (secondary) acute myeloid leukemia
(AML).
Data, independently validated, from AML patients with a FLT3
mutation demonstrated VYXEOS had a statistically significant
improvement in induction response rate (CR+CRi of 68.2% versus
25.0%; p=0.007). A benefit in induction response rate was seen in
both FLT3-ITD and FLT3-TKD patients.
|
Response Rate
(responders/number of patients)
|
|
VYXEOS
(CPX-351)
|
7+3
|
FLT3
mutated
|
15/22
(68.2%)
|
5/20
(25.0%)
|
FLT3-ITD
|
12/19
|
3/13
|
FLT3-TKD
|
3/3
|
2/7
|
An improvement in overall survival was also observed in FLT3
mutated patients with median overall survival of 10.25 months in
the VYXEOS arm compared to 4.55 months in the 7+3 arm. The
Hazard Ratio (HR) was 0.57 (p-value=0.093). In addition,
preliminary data on NPM1 and CEBPα mutations were presented showing
an improvement in response rate and overall survival in patients
with these mutations. Final data for NPM1 and CEBPα mutations
is expected to be presented at an upcoming medical conference.
"The improved response and survival observed in this
exploratory analysis for VYXEOS over 7+3
in molecularly-defined AML subsets from the Phase 3 trial
are promising, particularly for mutated FLT3 patients who
typically have a poor prognosis," said Bruno C. Medeiros, M.D., Associate Professor of
Medicine, Stanford University Medical
Center. "These clinical data corroborate previous ex
vivo results suggesting increased sensitivity of FLT3
mutated AML blasts to VYXEOS and supports ongoing and prospective
clinical studies in a broader range of AML cohorts."
Approximately 20-30% of AML patients harbor some form of FLT3
mutation. The significance of the mutation, in any given
patient, varies according to the nature of the mutation and the
context in which it occurs. The most common type of mutation is an
internal tandem duplication (ITD) mutation localized to a membrane
region of the receptor, while point mutations in the tyrosine
kinase domain (TKD) are less common. AML patients with a FLT3
mutation are believed to have a poorer prognosis than the overall
population diagnosed with AML.
"We continue to learn more from the Phase 3 trial about the
benefit of VYXEOS in AML patients," said Scott Jackson, Chief Executive Officer of
Celator Pharmaceuticals. "The results seen in patients with the
FLT3 mutation are encouraging and generated the hypothesis that
FLT3 mutated AML may be more sensitive to VYXEOS treatment and lead
to improved clinical benefit. Further clinical trials are warranted
in this patient population."
The company expects to submit a New Drug Application (NDA) for
VYXEOS with the U.S. Food and Drug Administration (FDA) by the end
of the third quarter of 2016 and submit a Marketing Authorization
Application (MAA) with the European Medicines Agency (EMA) in the
first quarter of 2017.
The clinical trial was conducted in partnership with The
Leukemia & Lymphoma Society® (LLS) through its Therapy
Acceleration Program (TAP), which has supported the clinical
development of VYXEOS beginning in Phase 2.
Phase 3 Trial Design
The randomized, controlled, Phase 3 trial (Protocol
NCT01696084), enrolled 309 patients at 39 sites in the United States and Canada, and compared VYXEOS to the
conventional cytarabine and daunorubicin treatment regimen
(commonly referred to as 7+3) as first-line therapy in older (60-75
years of age) patients with high-risk (secondary) AML. Patients
were stratified for age (60 to 69 and 70 to 75 years of age) and
AML type; treatment-related AML, AML with documented history of
myelodysplastic syndrome (MDS) with prior treatment with
hypomethylating agent therapy, AML with documented history of MDS
without prior hypomethlyating agent therapy, AML with a documented
history of chronic myelomonocytic leukemia (CMMoL), and de novo AML
with a karyotype characteristic of MDS.
Patients were randomized 1:1 to receive either VYXEOS or
7+3. Patients could receive one or two inductions, and
responding patients could receive one or two
consolidations. First induction for VYXEOS was
100u/m2; days 1, 3, and 5 by 90-minute infusion and for
the control arm was cytarabine 100mg/m2/day by
continuous infusion for 7 days and daunorubicin 60mg/m2
on days 1, 2, and 3 (7+3). Second induction for VYXEOS-treated
patients was 100u/m2 on days 1 and 3, and the control
arm was cytarabine 100mg/m2/day by continuous infusion
for 5 days and daunorubicin 60mg/m2 on days 1 and 2
(5+2).
Only patients with documented CR or CRi were eligible to receive
chemotherapy consolidation. Consolidation for VYXEOS-treated
patients was 65u/m2 on days 1 and 3 and the control arm
was cytarabine 100mg/m2/day by continuous infusion for 5
days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).
About VYXEOS
VYXEOS (cytarabine:daunorubicin) Liposome for Injection, also
known as CPX-351, is a nano-scale co-formulation of cytarabine and
daunorubicin at a synergistic 5:1 molar ration. VYXEOS
represents a novel approach to developing combinations of drugs in
which molar ratios of two drugs with synergistic anti-tumor
activity are encapsulated in a nano-scale liposome in order to
maintain the desired ratio following administration. The FDA
granted Breakthrough Therapy designation to VYXEOS for the
treatment of adults with therapy-related AML (t-AML) or AML with
myelodysplasia-related changes (AML-MRC). VYXEOS was granted
orphan drug status for the treatment of AML by the FDA and the
European Commission. VYXEOS was also granted Fast Track
designation for the treatment of elderly patients with secondary
AML by the FDA.
About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of
the blood characterized by the uncontrolled proliferation of
immature blast cells in the bone marrow. AML is generally a
disease of older adults, and the median age of a patient diagnosed
with AML is about 67 years. The American Cancer Society estimates
that there will be 19,950 new cases of AML and 10,430 deaths from
AML in the U.S. in 2016. In Europe the number of new cases is
estimated to be 18,000 and in Japan the number is 5,500. The Company
estimates that nearly 70 percent of AML patients are over the age
of 60, and approximately 75% are intermediate or high risk.
Furthermore, approximately half of those patients are considered
suitable for intensive treatment.
Even with current treatment, overall survival for AML is
poor. In patients over 60 years of age, the 5 year survival
rate is less than 10%. In high-risk (secondary) AML, overall
survival is lower, resulting in an acute need for new treatment
options for these patients.
About Celator Pharmaceuticals, Inc.
Celator Pharmaceuticals, Inc., with locations in Ewing, N.J., and Vancouver, B.C., is an oncology-focused
biopharmaceutical company that is transforming the science of
combination therapy, and developing products to improve patient
outcomes in cancer. Celator's proprietary technology platform,
CombiPlex®, enables the rational design and rapid evaluation of
optimized combinations of anti-cancer drugs, incorporating
traditional chemotherapies as well as molecularly targeted agents
to deliver enhanced anti-cancer activity. CombiPlex addresses
several fundamental shortcomings of conventional combination
regimens, as well as the challenges inherent in combination drug
development, by identifying the most effective synergistic molar
ratio of the drugs being combined in vitro, and fixing this
ratio in a nano-scale drug delivery complex to maintain the
optimized combination after administration and ensuring exposure of
this ratio to the tumor. Celator's lead product is VYXEOS™
(also known as CPX-351), a nano-scale liposomal formulation of
cytarabine:daunorubicin that has completed a Phase 3 trial for the
treatment of acute myeloid leukemia. Celator has also conducted
clinical development on CPX-1, a nano-scale liposomal formulation
of irinotecan:floxuridine studied in colorectal cancer; and have a
preclinical stage product candidate, CPX-8, a hydrophobic docetaxel
prodrug nanoparticle formulation. More recently, the company
has advanced its CombiPlex platform and broadened its application
to include molecularly targeted therapies. For more information,
please visit Celator's website at www.celatorpharma.com.
Information on ongoing trials is available at
www.clinicaltrials.gov.
Forward-Looking Statements:
To the extent that statements contained in this press release
are not descriptions of historical facts regarding Celator, they
are forward-looking statements reflecting the current beliefs and
expectations of management made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
Words such as "may," "will," "expect," "anticipate," "estimate,"
"intend," and similar expressions (as well as other words or
expressions referencing future events, conditions or circumstances)
are intended to identify forward-looking statements. Examples of
forward-looking statements contained in this press release include,
among others, statements regarding the safety, potential efficacy,
therapeutic potential and commercial potential of VYXEOS™ (also
known as CPX-351), our expectations regarding the timing of our
regulatory filings, our expectations regarding our research and
development programs and advancing our CombiPlex platform and the
potential to establish research and development collaborations
applying our proprietary technologies with other
biotechnology/pharmaceutical companies. Forward-looking statements
in this release involve substantial risks and uncertainties that
could cause our development programs, future results, or
achievements to differ significantly from those expressed or
implied by the forward-looking statements. Such risks and
uncertainties include, among others, the uncertainties inherent in
the conduct of clinical studies, whether clinical study results
obtained to date will be predictive of future results, whether the
final results of our clinical studies will be supportive of
regulatory approval to market VYXEOS and other matters that could
affect the commercial potential of our drug candidates. Celator
undertakes no obligation to update or revise any forward-looking
statements. For a further description of the risks and
uncertainties that could cause actual results to differ from those
expressed in these forward-looking statements, as well as risks
relating to the business of the company in general, see Celator's
Form 10-K for the year ended December 31,
2015, subsequent reports on Form 10-Q and 8-K, and other
filings by the company with the U.S. Securities and Exchange
Commission.
Contacts:
Media:
Sam Brown, Inc.
Mike Beyer, 312-961-2502
mikebeyer@sambrown.com
Investors:
The Trout Group
Peter Rahmer, 646-378-2973
prahmer@troutgroup.com
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