Full Press Release Details
Announces PRESENTATION OF RESULTS FROM PHASE 3
STUDY AT ASH ANNUAL MEETING
Berkeley Heights, NJ, December 12,
2017 - Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical
company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious
disorders, today announced results from the Company's Phase 3 SEAMLESS study. Cyclacel had previously announced top-line results
from its Phase 3 SEAMLESS study in February 2017. The study enrolled elderly patients with newly diagnosed acute myeloid leukemia
(AML) and compared alternating cycles of decitabine and sapacitabine versus decitabine. Data were reported at an oral presentation
on Monday, December 11, at 6:45 PM EST at the 59th American Society of Hematology Annual Meeting in Atlanta, Georgia.
"Although the study did not reach
its primary endpoint of superiority in survival, we are encouraged by the higher complete remission rate on the sapacitabine-decitabine
arm, especially in the subgroup with low white blood cell count; additional analysis of the data should be pursued," said
Hagop Kantarjian, M.D., Professor and Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and chair
"We are pleased to report detailed
results of the SEAMLESS study, which as previously announced, did not reach its primary endpoint," said Spiro Rombotis, President
and Chief Executive Officer of Cyclacel. "We believe that the subgroup results have defined a patient population for whom
the decitabine-sapacitabine regimen may represent an improvement over low intensity treatment by decitabine alone. We plan to discuss
the data, the statistical robustness of the subgroup results and the optimal baseline peripheral white blood cell (WBC) cutpoint
with European and US regulatory authorities and will provide updates as appropriate. We are grateful to the patients, their families
and the investigators for their contributions to this large study. In parallel, we are progressing our other clinical programs
in transcriptional regulation with CYC065 and DNA damage response with sapacitabine-seliciclib in biomarker-selected patients with
solid tumors, such as those with BRCA mutations or resistance to existing cancer therapies."
Study Design & Intent-to-Treat
The randomized, open label, Phase 3
SEAMLESS study enrolled 482 patients, aged 70 years or older, with newly diagnosed AML who were not candidates for or refused intensive
therapy at 110 US and EU sites. Patients were stratified by WBC, antecedent hematologic disorder (AHD), and marrow blasts, and
randomized 1:1 to receive either intravenous decitabine administered in alternating cycles with oral sapacitabine versus intravenous
The trial did not meet its primary
endpoint of demonstrating statistically significant improvement in overall survival. A higher complete remission (CR) rate, a secondary
endpoint, was observed on the decitabine-sapacitabine arm (17% versus 11%). Other endpoints and safety were similar between the
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Prespecified Subgroup Analysis
In the less than 10,000 WBC subgroup
(n=319) a trend towards improved overall survival (median 8.0 versus 5.8 months, HR=0.84 [0.66, 1.06], p=0.14) favoring decitabine-sapacitabine
and a significantly higher CR rate (21.0% versus 8.6%, p=0.0017) was achieved on decitabine-sapacitabine.
In the 10,000 or more WBC subgroup
(n=163) significantly better overall survival (median 3.8 versus 5.5 months, HR=1.57 [1.12, 2.19], p=0.007) was observed on decitabine.
A trend in CR rate (8.3% versus 15.2%, p=0.18) favoring decitabine was observed but it did not reach statistical significance.
In the subgroup with prior AHD (n=136)
a significantly higher CR rate (16.7% versus 5.7%, p=0.0398) was achieved on decitabine-sapacitabine. There was a numerical difference
in median survival (6.4 versus 5.0 months, HR=0.85 [0.59, 1.24], p=0.41) favoring decitabine-sapacitabine but overall survival
did not reach statistical significance.
In the subgroup without prior AHD (n=346)
there was a numerical difference in median survival (5.9 versus 6.7 months, HR=1.08 [0.86, 1.35], p=0.52) favoring decitabine and
CR rate (16.6% versus 12.9%) favoring decitabine-sapacitabine but neither reached statistical significance.
In the subgroup with other than unfavorable
cytogenetics (n=288) there was a numerical difference in median survival (8.2 versus 5.7 months, HR=0.89 [0.69, 1.15], p=0.38)
and CR rate (19.9% versus 11.6%, p=0.16) favoring decitabine-sapacitabine but neither reached statistical significance.
In the subgroup with unfavorable cytogenetics
(n=194) there was a numerical difference in median survival (3.8 months versus 5.7 months, HR=1.27 [0.94, 1.73], p=0.12) favoring
decitabine but overall survival did not reach statistical significance. There was a numerical difference in CR rate favoring decitabine-sapacitabine
(12.0% versus 9.6%) but it did not reach statistical significance.
In the subgroup of patients with below
50% and with 50% or higher bone marrow blasts there were no statistically significant differences in overall survival between the
The presentation (abstract 891), titled
"Results of a Phase 3 Study of Elderly Patients with Newly Diagnosed AML Treated with Sapacitabine and Decitabine Administered
in Alternating Cycles," is available on the Cyclacel website at www.cyclacel.com.
Sapacitabine (CYC682), an orally-available
nucleoside analogue, is currently being studied in an ongoing, extension of a Phase 1 study evaluating a combination regimen of
sapacitabine and seliciclib, a first generation CDK inhibitor. Parts 1 and 2 of the study evaluated approximately 90 patients with
advanced cancers. Part 3 is ongoing in patients with BRCA positive, breast, ovarian and pancreatic cancer. Over 1,000 patients
with hematological malignancies and solid tumors have received sapacitabine.
AML is a rapidly progressing cancer
of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. The American Cancer Society
estimates there will be approximately 21,380 new cases of AML and approximately 10,590 deaths from AML in the U.S. in 2017. AML
is generally a disease of older adults and the median age is about 67 years. Newly diagnosed elderly patients with poor prognostic
risk factors typically die within one year.
About Cyclacel Pharmaceuticals,
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 transcriptional regulation program is evaluating CYC065, a CDK
inhibitor, in patients with advanced cancers. The DNA damage response program is evaluating a sequential regimen of sapacitabine
and seliciclib, a CDK inhibitor, in patients with BRCA positive, advanced solid cancers. 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.