- Study did not reach statistically significant
improvement in the primary endpoint of overall survival -
Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP)
("Cyclacel" or the "Company"), a biopharmaceutical company
developing oral therapies that target the various phases of cell
cycle control for the treatment of cancer and other serious
disorders, today reported top-line results from the pivotal Phase 3
SEAMLESS study in elderly patients aged 70 years or older with
newly diagnosed acute myeloid leukemia (AML), who are not
candidates for or have refused intensive induction chemotherapy.
The trial did not meet its primary endpoint of
demonstrating statistically significant improvement in overall
survival (OS) for the experimental arm versus an active
control. An improved rate of complete remission (CR), a
secondary endpoint, was observed in patients who had discontinued
therapy at the time of analysis. Other endpoints and safety were
similar between the arms. In the stratified subgroup of patients
with low baseline peripheral white blood cell count, comprising
approximately two-thirds of the study’s population, an improvement
in OS was observed for the experimental arm. The opposite was true
for patients with high white blood cell count. Full results from
the SEAMLESS study will be submitted for presentation at an
upcoming medical conference.
“The results of the SEAMLESS Phase 3 study
demonstrate that sapacitabine is active and safe in elderly AML
patients,” said Hagop Kantarjian M.D., Professor and Chair,
Department of Leukemia, The University of Texas MD Anderson Cancer
Center, and chair of the SEAMLESS study. “Although the
experimental arm of alternating decitabine-sapacitabine did not
reach statistically significant superiority in overall survival, it
is remarkable that an improvement in complete remission rate was
observed. Additional analysis of stratified and exploratory
subgroups is warranted to identify patients who are most likely to
benefit from treatment with the experimental arm.”
"We are disappointed not to have reached the
primary endpoint of SEAMLESS. Nevertheless, the improvement in CR
rate and similar safety profile are encouraging. We plan to discuss
the data with European and US regulatory authorities once subgroup
analyses are completed over the next few months and will report our
further plans as they develop. We are grateful to the clinical
investigators, and especially the patients and their families, for
their contributions to this large study,” said Spiro Rombotis,
President and Chief Executive Officer of Cyclacel. “In parallel
with data analysis and regulatory discussions, we will reevaluate
our continued investment in sapacitabine in hematological
malignancies. Our clinical development strategy in oncology will
now concentrate on our two ongoing, clinical programs in DNA damage
response and transcriptional regulation, which include our area of
historical expertise in CDK inhibitors. These programs target
biomarker-selected patients, such as those with BRCA mutations or
resistance to existing cancer therapies. Our cash resources are
projected to fund these activities and operations through the end
of 2018.”
Clinical Development
Strategy
For the past few years the Company has been
progressing clinical investigation of two programs in parallel with
the SEAMLESS study based on promising scientific and preclinical
data. The DNA damage response program is evaluating an
orally-administered, sequential regimen of sapacitabine and
seliciclib, a CDK2/9 inhibitor, in patients with BRCA positive,
advanced solid cancers. The transcriptional regulation program is
evaluating CYC065, a CDK2/9 inhibitor, in patients with advanced
cancers with emphasis on downregulation of the Mcl-1 biomarker.
DNA Damage Response Program
Phase 1 data from this program in 67 patients
with various advanced cancers were reported at an oral presentation
during the 2016 American Society of Clinical Oncology (ASCO) Annual
Meeting. Antitumor activity with durable clinical responses was
demonstrated in a subgroup of 45 patients with breast, ovarian and
pancreatic cancers who tested positive for BRCA mutations. A cohort
of breast cancer patients who carry BRCA mutations is being
enrolled as an expansion of this study. A further cohort is in
preparation which will evaluate alternative dosing schedules and
collect more data in BRCA positive patients with solid tumors other
than breast cancer. The DNA Damage Response program is benefiting
from the historical experience with sapacitabine in hematological
malignancies, understanding of its mechanism of action and sizable
patient safety database.
Transcriptional Regulation
Program
Cyclacel’s second generation CDK2/9 inhibitor,
CYC065, is being evaluated in an ongoing, first-in-human, Phase 1
trial in patients with advanced solid tumors. In addition to
determining safety and recommended dosing for Phase 2, the study
aims to investigate CYC065’s effects on the Mcl-1 biomarker, which
is implicated in the evolution of resistance in cancer. The study
has reached the seventh dose escalation level without observations
of serious toxicity. Evidence of target engagement of prolonged
Mcl-1 suppression in peripheral blood cells was observed in patient
samples from the study, as well as decreases in kinase substrate
phosphorylation and increases in PARP cleavage, which were
consistent with the Company’s preclinical data.
Similar to palbociclib, the first CDK inhibitor
approved by FDA in 2015, CYC065 may be most useful as a therapy for
patients with both liquid and solid tumors in combination with
other anticancer agents, including Bcl-2 antagonists, such as
venetoclax, or HER2 inhibitors, such as trastuzumab.
Conference Call and Webcast
Information:
Cyclacel will hold a conference call on February
23, 2017 at 9:00 a.m. Eastern Time to discuss the Company’s plans
with regard to SEAMLESS. Conference call and webcast details are as
follows:
US/Canada call: (877) 493-9121/ international
call: (973) 582-2750US/Canada archive: (800) 585-8367 /
international archive: (404) 537-3406Code for live and archived
conference call is: 77162157
For the live and archived webcast, please visit
the Corporate Presentations and Events page on the Cyclacel website
at www.cyclacel.com. The webcast will be archived for 90 days and
the audio replay for 7 days.
About SEAMLESS
The Phase 3, randomized trial compared an
investigational arm of oral sapacitabine administered in
alternating cycles with intravenous decitabine compared with an
active control arm of intravenous decitabine administered alone.
The trial was conducted at 110 US and EU sites and randomized 491
patients, over an approximately three year period. Stratification
factors at randomization were antecedent hematologic disorders,
baseline peripheral white blood cells and baseline bone marrow
blasts. In December 2014, the study’s monitoring committee
determined after an interim analysis that the futility boundary was
crossed. In accordance with the committee’s recommendations, the
Company continued to follow up enrolled patients to maturity.
About Sapacitabine
Sapacitabine (CYC682), an orally-available
nucleoside analogue, acts through a novel DNA single-strand
breaking mechanism, leading to production of DNA double strand
breaks (DSBs) and/or checkpoint activation. Unrepaired DSBs cause
cell death. Repair of sapacitabine-induced DSBs is dependent on the
homologous recombination repair (HRR) pathway. Both sapacitabine
and its major metabolite, CNDAC, have demonstrated potent
anti-tumor activity in preclinical studies.
In addition to the SEAMLESS Phase 3 study in
elderly patients with AML who were unfit or refused intensive
induction chemotherapy, other Phase 2 studies evaluated
sapacitabine in patients with myelodysplastic syndromes (MDS),
cutaneous T cell lymphoma (CTCL) and non-small cell lung cancer
(NSCLC). The US FDA and the European Medicines Agency have
designated sapacitabine as an orphan drug for the treatment of both
AML and MDS. Sapacitabine is part of Cyclacel's pipeline of small
molecule drugs designed to target and stop uncontrolled cell
division.
About Cyclacel Pharmaceuticals,
Inc.
Cyclacel Pharmaceuticals is a clinical-stage
biopharmaceutical company using cell cycle, transcriptional
regulation and DNA damage response biology to develop innovative,
targeted medicines for cancer and other proliferative diseases.
Cyclacel's DNA damage response program is evaluating a sequential
regimen of sapacitabine and seliciclib, a CDK inhibitor, in
patients with BRCA positive, advanced solid cancers. The
transcriptional regulation program is evaluating CYC065, a CDK
inhibitor, in patients with advanced cancers. Cyclacel is analyzing
stratified and exploratory subgroups from a Phase 3 study of
sapacitabine in elderly patients with AML. Cyclacel's strategy is
to build a diversified biopharmaceutical business focused in
hematology and oncology based on a pipeline of novel drug
candidates. For additional information, please visit
www.cyclacel.com.
Forward-looking Statements
This news release contains certain
forward-looking statements that involve risks and uncertainties
that could cause actual results to be materially different from
historical results or from any future results expressed or implied
by such forward-looking statements. Such forward-looking statements
include statements regarding, among other things, the efficacy,
safety and intended utilization of Cyclacel's product candidates,
the conduct and results of future clinical trials, plans regarding
regulatory filings, future research and clinical trials and plans
regarding partnering activities. Factors that may cause actual
results to differ materially include the risk that product
candidates that appeared promising in early research and clinical
trials do not demonstrate safety and/or efficacy in larger-scale or
later clinical trials, trials may have difficulty enrolling,
Cyclacel may not obtain approval to market its product candidates,
the risks associated with reliance on outside financing to meet
capital requirements, and the risks associated with reliance on
collaborative partners for further clinical trials, development and
commercialization of product candidates. You are urged to consider
statements that include the words "may," "will," "would," "could,"
"should," "believes," "estimates," "projects," "potential,"
"expects," "plans," "anticipates," "intends," "continues,"
"forecast," "designed," "goal," or the negative of those words or
other comparable words to be uncertain and forward-looking. For a
further list and description of the risks and uncertainties the
Company faces, please refer to our most recent Annual Report on
Form 10-K and other periodic and other filings we file with the
Securities and Exchange Commission and are available at
www.sec.gov. Such forward-looking statements are current only as of
the date they are made, and we assume no obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
© Copyright 2017 Cyclacel Pharmaceuticals, Inc.
All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks
of Cyclacel Pharmaceuticals, Inc.
Contacts
Company:
Paul McBarron, (908) 517-7330, pmcbarron@cyclacel.com
Investor Relations:
Russo Partners LLC, Alexander Fudukidis, (646) 942-5632, alex.fudukidis@russopartnersllc.com
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