Cyclacel Reports Updated Phase 2 Survival Data of Sapacitabine for MDS
Nearly Doubles Expected Median Survival of Older Patients With MDS Who Failed
BERKELEY HEIGHTS, N.J., April 30, 2013 (GLOBE NEWSWIRE) -- Cyclacel
Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) (Cyclacel or the Company),
announced updated median overall survival data from an ongoing, multicenter,
Phase 2 randomized trial of oral sapacitabine capsules, the Company's lead
product candidate, in older patients with intermediate-2 or high-risk
myelodysplastic syndromes (MDS) after treatment failure of front-line
hypomethylating agents, such as azacitidine (Vidaza®) and/or decitabine
(Dacogen®). Median overall survival to date for all 63 patients treated is
approximately 9 months.Median overall survival for each of the three
randomization schedules is approximately 10 months for Arm G, 10 months for
Arm H and 8 months for Arm I.The 30-day mortality for all patients is 5%.
"The updated survival data from this study in MDS patients after treatment
failures of hypomethylating agents continue to be impressive based on our
experience," said Guillermo Garcia-Manero, M.D., Chief of the Section of
Myelodysplastic Syndromes and Professor, Department of Leukemia, The
University of Texas MD Anderson Cancer Center and an investigator for the
study. "Sapacitabine's oral administration and low 30-day mortality suggest
that it may become a new treatment standard for older patients with MDS."
"There is a dearth of treatment options for MDS patients after failing
front-line therapies. The updated survival data with sapacitabine as a single
agent in MDS confirm our previous experience with the drug," said Hagop
Kantarjian, M.D., Chairman & Professor, Department of Leukemia, The University
of Texas MD Anderson Cancer Center and principal investigator for the study.
"Median survival for patients with intermediate-2 or high-risk MDS following
treatment failures of hypomethylating agents is 4.3 to 5.6 months.We urgently
need new therapeutics for these patients with the potential of controlling the
disease and offering high quality of life."
The updated median overall survival for all three arms is 259 days or
approximately 9 months.The median overall survival for each arm was 291 days
or approximately 10 months for Arm G, 290 days or approximately 10 months for
Arm H, and 227 days or approximately 8 months for Arm I.Median number of
cycles was 3. Approximately 43% of patients received 4 or more cycles.Median
follow-up is 524 days and 13 patients are still alive. Longer follow-up is
needed to assess 1-year survival and overall survival of each arm.
Topline median survival data were previously reported at two separate sessions
at The Eighth Annual Hematologic Malignancies 2012 Conference held on October
10-14, 2012, in Houston, Texas.
The open-label, multi-center, Phase 2 study randomized 63 patients aged 60
years or older with MDS of intermediate-2 (n=50) or high-risk (n=13)
classification by the International Prognostic Scoring System (IPSS) at study
entry to receive sapacitabine every 4 weeks on one of 3 dosing schedules: 200
mg twice daily for 7 days (Arm G), 300 mg once daily for 7 days (Arm H), or
100 mg once daily for 5 days per week for 2 weeks (Arm I). Eligible patients
must be aged 60 years or older with intermediate-2 or high-risk MDS previously
treated with hypomethylating agents and 6%-19% blasts in their bone marrow,
ECOG performance status 0-2, adequate renal and hepatic function. The primary
efficacy endpoint is 1-year survival with the objective of identifying a
dosing schedule that produces a better 1-year survival rate in the event that
all three dosing schedules are active.Median age was 73. Thirty-nine patients
had 10-19% blasts in their bone marrow. All patients in the study progressed
after receiving either azacitidine and/or decitabine. Eighteen patients were
double refractory as they had received both agents.
About Myelodysplastic Syndromes (MDS)
MDS is a family of clonal myeloid neoplasms, or malignancies of the blood,
caused by the failure of blood cells in the bone marrow to develop into mature
cells. Patients with MDS typically suffer from bone marrow failure and
cytopenias, or reduced counts of platelets, red and white blood cells. The
exact incidence and prevalence of MDS are unknown because it can go
undiagnosed and a national survey canvassing both hospitals and office
practitioners has not been completed. Some estimates place MDS incidence at
15,000 to 20,000 new cases each year in the US alone with some authors
estimating incidence as high as 30,000 to 46,000. Literature evidence suggests
that there is a rising incidence of MDS as the age of the population increases
with the majority of patients aged above 60 years.
Median survival for patients with intermediate-2 or high-risk disease, as
defined by the International Prognostic Scoring System (IPSS), is 4.3 to 5.6
months. Patients with high IPSS scores also have a high probability of
experiencing transformation of their MDS into AML, an aggressive form of blood
cancer with typically poor survival.
Sapacitabine (CYC682), an orally-available nucleoside analogue, is being
studied in SEAMLESS, an ongoing, Phase 3, registration-directed trial in
elderly patients aged 70 years or older with newly diagnosed AML who are not
candidates for or have refused induction chemotherapy. Sapacitabine is in
Phase 2 trials in patients with hematological malignancies, including AML,
myelodysplastic syndromes (MDS), cutaneous T-cell lymphoma (CTCL), chronic
lymphocytic leukemia, small lymphocytic lymphoma, and also non-small cell lung
cancer (NSCLC), and a Phase 1 trial with Cyclacel's oral seliciclib in
patients with advanced solid tumors. Sapacitabine 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 (HR) DNA repair pathway. Both sapacitabine and CNDAC, its major
metabolite, have demonstrated potent anti-tumor activity in preclinical
Over 650 patients have received sapacitabine in clinical studies in patients
with AML, MDS, CTCL, NSCLC, hematological malignancies and solid tumors. At
the 2012 American Society of Hematology (ASH) Annual Meeting, data from the
pilot study and lead-in phase of SEAMLESS showed promising response rate,
overall survival and low 30- and 60-day mortality in elderly patients with AML
aged 70 years or older receiving sapacitabine alternating with decitabine.
Data, presented at The Eighth Annual Hematologic Malignancies 2012 Conference,
from an ongoing, multicenter, Phase 2 randomized trial of single-agent oral
sapacitabine capsules in older patients with intermediate-2 or high-risk
myelodysplastic syndromes (MDS) after treatment failure of front-line
hypomethylating agents, such as azacitidine and/or decitabine, showed
sapacitabine nearly doubled expected median survival of elderly patients with
MDS after front-line therapy failure. Cyclacel is developing a pivotal trial
plan for sapacitabine in the MDS indication.Results from a randomized Phase
2, single-agent study of sapacitabine, including promising 1-year survival in
elderly patients with AML aged 70 years or older, were published in The Lancet
Oncology in November 2012. In a Phase 1 study, sapacitabine, in combination
with Cyclacel's seliciclib, showed antitumor activity in cancer patients with
HR pathway defects including carriers of BRCA mutations. The 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
About Cyclacel Pharmaceuticals, Inc.
Cyclacel is a biopharmaceutical company developing oral therapies that target
the various phases of cell cycle control for the treatment of cancer and other
serious diseases. Sapacitabine, Cyclacel's most advanced product candidate, is
the subject of SEAMLESS, a Phase 3 trial being conducted under an SPA with the
FDA as front-line treatment for acute myeloid leukemia (AML) in the elderly,
and other studies for myelodysplastic syndromes (MDS), chronic lymphocytic
leukemia (CLL) and solid tumors including breast, lung, ovarian and pancreatic
cancer and in particular those carrying BRCA mutations. Cyclacel's strategy
is to build a diversified biopharmaceutical business focused in hematology and
oncology based on a development pipeline of novel drug candidates. Please
visit www.cyclacel.com for additional information.
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
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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 2013 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The
Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.
Vidaza® is a registered trademark of Celgene Corporation. Dacogen® is a
registered trademark used by Eisai Inc. under license from Astex
CONTACT: Contact for Cyclacel Pharmaceuticals, Inc.
Investors/Media: Corey Sohmer,
(908) 517-7330, firstname.lastname@example.org
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