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Study Provides Support for SEAMLESS, an Ongoing, Phase 3, Registration-Directed Trial in Elderly Patients With Newly Diagnosed AML
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Updated Survival Data From a Pilot Study and Lead-In Phase of SEAMLESS to be Presented at the 2012 Annual Meeting of the American Society of Hematology
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BERKELEY HEIGHTS, N.J., Nov. 1, 2012 (GLOBE NEWSWIRE) -- Cyclacel
Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) (Cyclacel or the
Company), today announced the publication of results from a Phase 2
randomized trial of single-agent sapacitabine in elderly patients
aged 70 years or older with newly diagnosed acute myeloid leukemia
(AML) or AML in first relapse. The study, published in The Lancet
Oncology, demonstrates the safety and efficacy of sapacitabine in
this patient population.
"We are pleased to report that Phase 2 data for sapacitabine in
AML has been published in a prestigious peer-reviewed journal,"
said Spiro Rombotis, President and Chief Executive Officer of
Cyclacel. "The data provide support for SEAMLESS, our ongoing,
Phase 3, registration-directed study in elderly patients with newly
diagnosed AML. We will provide an update on patient enrollment in
SEAMLESS during our third quarter conference call and present
updated survival data from the pilot study and lead-in phase of
SEAMLESS at the upcoming American Society of Hematology 2012 annual
meeting in December. We also look forward to reaching the second
planned periodic safety review of SEAMLESS in the near future. In
addition to our AML programs, we are committed to exploring with
the FDA next steps for sapacitabine in older patients with
intermediate-2 or high-risk myelodysplastic syndromes (MDS) after
failure of front-line therapy based on encouraging survival
demonstrated in recently disclosed Phase 2 data.
If Phase 3 trials are successful, sapacitabine could emerge as the
first oral drug for the treatment of AML, and possibly, MDS."
The Phase 2 study enrolled and treated between December 27, 2007
and April 21, 2009, a total of 105 patients aged 70 years or above
with untreated or first relapse AML. The median age of patients was
77 years (range 70--91). The group was comprised of a randomized
cohort of 60 patients and an expanded, non-randomly assigned cohort
enrolling a further 45 patients. Of the 105 patients, 86 were
previously untreated and 19 in first relapse. Approximately 50% of
patients had AML de novo and 50% had AML preceded by antecedent
hematological disorder (AHD), such as MDS or myeloproliferative
disease, or treatment-related AML.
All but one enrolled patients had intermediate or unfavorable
cytogenetics. The randomized cohort of patients were randomly
assigned to one of three dosing schedules: 200 mg twice a day for 7
days (group A); 300 mg twice a day for 7 days (group B); and 400 mg
twice a day for
3 days each week for 2 weeks (group C). All schedules were given in
28 day cycles.
The 3-day dosing schedule in group C was selected for further clinical development in elderly patients with untreated AML. This decision was based on the schedule's overall efficacy profile, which included a 1-year survival rate of 30%, median overall survival of 213 days and durable complete remissions (CRs) in 25% of patients. The median overall survival of patients from all groups who achieved CR was 525 days (95% C.I. 192--798).
The most common grade 3--4 adverse events regardless of causality were anemia, neutropenia, thrombocytopenia, febrile neutropenia and pneumonia. Seven deaths were thought to be probably or possibly related to sapacitabine treatment. Approximately 31% of all patients received sapacitabine for at least 4 cycles.
Journal Citation
Hagop Kantarjian, Stefan Faderl, Guillermo Garcia-Manero, Selina Luger, Parameswaran Venugopal, Lori Maness, Meir Wetzler, Steven Coutre, Wendy Stock, David Claxton, Stuart L Goldberg, Martha Arellano, Stephen A Strickland, Karen Seiter, Gary Schiller, Elias Jabbour, Judy Chiao, William Plunkett, Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study, The Lancet Oncology, Volume 13, Issue 11, Pages 1096 - 1104, November 2012.
The journal paper can be accessed at:
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%297
0436-9/fulltext or by using doi:10.1016/S1470-2045(12)70436-9.
About Acute Myeloid Leukemia (AML)
AML is a cancer of the blood cells that progresses rapidly and
if not treated, could be fatal in a few months. AML is generally a
disease of older people and is uncommon before the age of 40. The
average age of a patient with AML is about 67 years. There are more
than 12,300 new cases of AML, of which about half are elderly aged
70 years or older.
Nearly 9,000 deaths are caused by this cancer each year in the
United States. A review of The University of Texas MD Anderson
Cancer Center's historical experience with front-line intensive
induction chemotherapy for AML patients aged 70 years or older
demonstrated that while 45% achieved a complete remission, median
overall survival was only 4.6 months and was associated with a
4-week death rate of 26% and a 8-week death rate of 36%
(Kantarjian, H, et al, Blood,
doi:10.1182/blood-2010-03-276485).
About sapacitabine and SEAMLESS
Sapacitabine (CYC682), an orally-available nucleoside analogue,
is currently being studied in 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.
SEAMLESS is being conducted under a Special Protocol Assessment
(SPA) agreement that Cyclacel reached with the US Food and Drug
Administration (FDA). Sapacitabine is also the subject of Phase 2
trials in patients with hematological malignancies, including MDS,
cutaneous T-cell lymphoma, chronic lymphocytic leukemia and small
lymphocytic lymphoma, and non-small cell lung cancer, a Phase 1
trial in combination with seliciclib in patients with advanced
solid tumors, and an investigator-led, Phase 2/3 study ("LI-1
Trial") comparing sapacitabine to low dose cytarabine as front-line
treatment of elderly patients with AML or high risk MDS unfit for
intensive chemotherapy.
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 DNA repair (HRR) pathway. Both sapacitabine and
CNDAC, its major metabolite, have demonstrated potent anti-tumor
activity in preclinical studies.
Over 500 patients have received sapacitabine in Phase 2 studies
in AML, MDS, CTCL and NSCLC and Phase 1 studies in hematological
malignancies and solid tumors. At the 2009 Annual Meeting of the
American Society of Hematology (ASH), Cyclacel reported data 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. At the 2011 Annual Meeting of the American Society
of Clinical Oncology (ASCO), Cyclacel reported data from a pilot
Phase 1/2 study including promising response rate, low 4-week and
8-week mortality in elderly patients with AML aged
70 years or older receiving sapacitabine alternating with
decitabine.
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 division.
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
oral capsules is in the SEAMLESS Phase 3 trial being conducted
under an SPA with the FDA as front-line treatment of acute myeloid
leukemia (AML) in the elderly, Phase 2 studies for myelodysplastic
syndromes (MDS) and solid tumors including lung cancer and in
investigator-led studies including a Phase
2/3 study comparing sapacitabine to low dose cytarabine as
front-line treatment of elderly patients with AML or high risk MDS
unfit for intensive chemotherapy and a Phase 2 study in chronic
lymphocytic leukemia. Cyclacel's pipeline includes seliciclib oral
capsules in Phase 2 studies for the treatment of lung cancer and
nasopharyngeal cancer and in a Phase 1 trial in combination with
sapacitabine.
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.
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.
(C) Copyright 2012 Cyclacel Pharmaceuticals, Inc. All Rights
Reserved.
The Cyclacel logo and Cyclacel(R) are trademarks of Cyclacel
Pharmaceuticals, Inc.
CONTACT: Cyclacel Pharmaceuticals, Inc.
Investors/Media:
Corey Sohmer
(908) 517-7330
csohmer@cyclacel.com
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Posted: November 2012
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