Interim Data From Phase 2 Trial of AC220 Monotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia With FLT3-ITD Activating Mutations

London (ots/PRNewswire) -

Ambit Biosciences Corporation and Astellas Pharma Inc. announced
today results from a planned interim analysis in an ongoing Phase 2
study evaluating AC220, a potent and selective FLT3 inhibitor. The
study is evaluating AC220 as an oral, once-a-day, monotherapy
treatment in acute myeloid leukemia (AML) in 240 patients with
FLT3-ITD activating mutations who have relapsed or are refractory to
other treatments, including chemotherapy and hematopoietic stem cell
transplant (HSCT). The data from this analysis was presented in an
oral session at the 16th Annual Congress of the European Hematology
Association (EHA) in London.

"AML patients who relapse or fail to respond to front-line
chemotherapy have poor prognoses, and patients that harbor mutations
in the FLT3 kinase are at an increased risk of disease relapse," said
Mark Levis, MD, PhD, Associate Professor, Oncology and Medicine,
Division of Hematologic Malignancies, Johns Hopkins, Baltimore,
Maryland, and an investigator in the Phase 2 study. "Once these
patients progress, the options available to them are limited, poorly
tolerated by the majority of patients, and often ineffective. We
presently lack an acceptable standard of care for AML patients with
FLT3-ITD activating mutations once they fail front-line treatment."

This interim analysis reported on clinical response and safety in
a subset of patients from the ongoing Phase 2 open-label, single-arm,
multi-center study conducted in the United States and Europe. Safety
data was reported on 62 patients and clinical response data was
reported on a group of 53 patients who met the efficacy evaluable
(EE) criteria. Patients included in the analysis were either greater
than or equal to 60 years old and relapsed or refractory to
first-line chemotherapy (Cohort 1, N=25), or greater than or equal to
18 years old and relapsed or refractory to second-line chemotherapy
or HSCT (Cohort 2, N=37).

The co-primary end points of the study are composite complete
remission rate (CRc) and complete remission rate in the first 84
days. CRc is defined as the sum of complete remission (CR), complete
remission with incomplete platelet recovery (CRp), and complete
remission with incomplete hematologic recovery (CRi). In the efficacy
evaluable population, there was a composite complete response (CRc)
rate of 45% for all patients, and 41% and 48% in Cohort 1 and Cohort
2, respectively, with the majority of CRc cases represented by CRi,
with no CRs observed, in the first 84 days. Notably, a CRc rate of
62% was achieved in patients who were refractory to the prior line of
treatment (N=16). Key secondary end points in the study include
duration of remission, rates of partial response, and overall
survival. The median duration of response for patients achieving a
CRc was 12.1 weeks and 10.6 weeks in all patients and Cohort 2,
respectively, with patients censored at the time of transplant.
Cohort 1 has yet to achieve a median duration of response. In
addition to the observed CRc rate, an additional 25% of efficacy
evaluable patients achieved a partial response (PR). The median
survival of efficacy evaluable patients was 24.7 weeks and 24.1 weeks
for all patients and Cohort 1, respectively. Cohort 2 has yet to
achieve a median survival, with 22 out of 31 patients alive at time
of analysis. More than one-third of the patients in the safety
population for Cohort 2 who had previously failed both induction
chemotherapy and salvage therapy transitioned to HSCT.

No treatment-related deaths have been reported at the time of the
analysis. The most common treatment-related adverse events included
nausea, vomiting, fatigue, and febrile neutropenia. Several cases of
asymptomatic QTc prolongation were reported early in the study, but
most resolved following a dose adjustment, and no Grade 4 cases have
been reported. Management of other adverse events is also being
explored with dose modifications in the ongoing study.

About AC220

AC220 is being developed in collaboration between Ambit
Biosciences and Astellas Pharma Inc., and is a novel, potent, highly
selective, orally bioavailable FMS-like tyrosine kinase-3 (FLT3)
inhibitor. AC220 is currently under evaluation in a Phase 2 clinical
trial as mono-therapy treatment for adult and elderly patients with
relapsed/refractory AML that have an internal tandem duplication
(ITD) mutation in the FLT3 gene. AML is one of the most common types
of blood cancers in adults, with ITD mutations in the FLT3 gene
occurring in 25-30 percent of AML patients. FLT3 ITD mutations confer
poor prognosis, with early relapse and lower survival following
treatment with existing therapies, including chemotherapy and
hematopoietic stem cell transplant.

About AML

Acute myeloid leukemia is a form of blood cancer. According to
the American Cancer Society, approximately 13,000 adults were newly
diagnosed with AML in 2009 in the United States with approximately
9,000 expected to die of the disease in that year. 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 67 and median survival for these
patients is less than six months. The five-year survival rate for all
AML patients is less than 15 percent. According to a report from
Decision Resources, the U.S. AML market is expected to more than
double by 2015.

About the Ambit/Astellas Collaboration

In December 2009, Ambit and Astellas entered into a global
strategic partnership agreement to jointly research, develop and
commercialize FLT3 kinase inhibitors in multiple indications,
including the lead investigational compound, AC220. The companies are
presently evaluating AC220 in a Phase 2 clinical trial in relapsed
and refractory AML patients that have the internal tandem duplication
(ITD) mutation in the FLT3 gene. The companies are also collaborating
on a comprehensive development program to explore the utility of
AC220 in other AML patient subpopulations. Additionally, the
companies are collaborating on a research and development program for
additional FLT3 inhibitors for a variety of oncology and non-oncology
indications. The companies share equal responsibility and expenses
for the development of products in the US and Europe, while Astellas
has sole responsibility in the rest of the world. Astellas will be
responsible for implementation of commercialization activities
worldwide. Ambit received a $40 million up-front payment upon
entering into the collaboration agreement, and is eligible to receive
up to $350 million in development milestone payments, undisclosed
sales milestones, and tiered, double-digit royalties on global
revenues. Ambit also has an option to co-promote products in the U.S.
where Astellas and Ambit share equally all profits and losses
generated from U.S. sales.

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company
engaged in the discovery and development of small molecule kinase
inhibitors for the treatment of cancer, inflammatory disease, and
other indications. Ambit's lead compound, AC220, is a novel, potent,
highly selective, orally bioavailable FMS-like tyrosine kinase-3
(FLT3) inhibitor, and is currently under clinical investigation in
patients with relapsed or refractory AML. Ambit is developing AC220
in collaboration with Astellas Pharma Inc. as part of a worldwide
agreement to jointly develop and commercialize FLT3 kinase inhibitors
in oncology and non-oncology indications. In addition to AC220,
Ambit's clinical pipeline includes AC480, an oral pan-HER inhibitor,
and AC430, an oral JAK2 inhibitor. Ambit also has a pipeline of
preclinical candidates which includes CEP-32496, a BRAF inhibitor
licensed to Cephalon.

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a
pharmaceutical company dedicated to improving the health of people
around the world through provision of innovative and reliable
pharmaceuticals. Astellas has approximately 16,000 employees
worldwide. The organization is committed to becoming a global
category leader in Urology, Immunology & Infectious Diseases,
Oncology, Neuroscience, and DM complications & Metabolic Diseases.
For more information on Astellas Pharma Inc., please visit our
website at http://www.astellas.com/en.

ots Originaltext: Astellas Pharma Europe Limited
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Contact:
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+1-858-334-2133; Doug Sherk/Jenifer Kirtland, EVC
Group,+1-415-896-6820; Media: Janine McCargo, EVC Group,
+1-646-528-4034; Astellas Pharma Inc: CorporateCommunications,
+81-3-3244-3201