Full Press Release Details
ANNOUNCES TOP-LINE RESULTS FROM PIVOTAL PHASE 3 SEAMLESS study
elderly patients with Acute myeloid leukemia
- Study did not reach statistically
significant improvement in the primary endpoint of overall survival -
- Improvement in secondary
endpoint of complete remission rate for the experimental arm -
- Conference call scheduled
today at 9:00 AM Eastern Time -
BERKELEY HEIGHTS, NJ, February 23,
2017 - 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."
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."
200 Connell Drive, Suite 1500, Berkeley Heights, NJ 07922,
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1 James Lindsay Place, Dundee, DD1 5JJ, UK Tel +44 1382
206 062 Fax +44 1382 206 067
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) 582-2750
US/Canada archive: (800) 585-8367 / international
archive: (404) 537-3406
Code for live and archived conference
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.
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.
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