Three-Year Follow-Up Data for SPRYCEL®? (dasatinib) 100 mg Once-Daily Demonstrates Faster and Deeper Responses Compared With Imatinib 400 mg in Patients With Newly Diagnosed Philadelphia+ Chronic Myel

Paris (ots/PRNewswire) -

Results Presented at 17th Congress of the European
Hematology Association

Bristol-Myers Squibb Company and Otsuka Pharmaceutical Europe
Ltd., today announced results from the 3-year follow-up of the
DASISION trial, which show that first-line treatment with SPRYCEL(R)
100 mg results infaster and deeper response rates compared with
Glivec(R) (imatinib) 400 mg [as defined by time to achieve Complete
Cytogenic Response (CCYR) or Major Molecular Response (MMR)].

Additionally, an exploratory landmark analysis of the study
suggests that patients with a deeper molecular response at three
months (defined as having a less than or equal to 10% BCR-ABL) show a
trend towards improved outcomes [such as Progression Free Survival
(PFS), Overall Survival (OS) and a lower risk of disease
transformation to Accelerated Phase or Blast Phase (AP/BP)] than the
patients who did not achieve this level of response at three months.
In this analysis, a deeper molecular response at three months was
achieved in 84% of dasatinib treated patients and 64% of imatinib
treated patients.[1]

"These findings are meaningful for newly diagnosed patients with
Chronic Myeloid Leukaemia (CML)," said Dr Andreas Hochhaus, Professor
of Internal Medicine and Head of the Department of Hematology and
Medical Oncology at the Jena University Hospital, Germany. "We are
now seeing that, in general, in CML an early and deep level of
response to treatment appears to be associated with a lower rate of
disease progression, and may be a promising indicator of better
long-term outcomes for patients. However, longer follow up is
needed."

Faster and Deeper Response by 3 Months

Research suggests that achieving a deep response earlier may
predict better long-term outcomes for patients.[2,3] In this 3 year
follow up of the DASISION study, the median time to response
(Complete Cytogenic Response, or CCYR) for dasatinib was 3.2 months
vs 6.0 months for imatinib. The median time to major molecular
response (MMR) was 15 vs 36 months, respectively.[4]By 3 years, MMR
was achieved in 68% of dasatinib treated and in 55% of imatinib
treated patients (p<0.0001)[1]

Additional exploratory analyses of the three year follow-up of
DASISION show:

- At 3 months, 84% of evaluable patients receiving dasatinib achieved less
than or equal to 10% BCR-ABL levels vs 64% of imatinib treated patients (p=0.0001)[1]
- A higher probability of 3-year PFS and OS was seen in patients achieving less
than or equal to 10% BCR-ABL compared to patients who had >10% BCR-ABL levels at 3
months[1]
- A lower level of transformation to AP/BP was seen in patients achieving less
than or equal to 10% BCR-ABL (dasatinib 3%: 6 of 198 patients; imatinib 2.6%: 4 of 154
patients) compared with patients who had >10% BCR-ABL levels at 3 months (dasatinib
13%: 5 of 37 patients; imatinib 13%: 11 of 85 patients) during this three year
follow-up.[1]

Continued Tolerability at 3 Years

The overall three-year dataalso showed that the safety profile
for dasatinib continues to be generally well-tolerated. Specifically,
the data show:

- Minimal changes in the tolerability profile at three years and with a
similar pattern of adverse events as previously observed[1]
- Rates of grade 3/4 non-hematologic AEs at 3 years in both arms remained low
(0-3%)[1]
- By the third year of treatment, 11% of patients discontinued dasatinib and 6%
discontinued imatinib due to intolerance[5]

Efficacy and safety Results in the European Subpopulation

Results of an exploratory analysis of the European subpopulation
(defined as patients treated in the European Union) of DASISION were
also presented at the 17th Congress of the European Hematology
Association. This analysis demonstrated that the efficacy and safety
profile of dasatinib in the European population (170 out of 519
included in DASISION) appeared comparable to that seen in the total
study population. The exploratory data for the EU subgroup show:

- Rates of MMR (65% for dasatinib and 56% for imatinib by 3 years)[5]
- Level of transformation; no patients treated with dasatinib vs 3 patients on
imatinib had transformation of CP-CML to AP/BP at or by 3 years [5]
- Tolerability generally consistent with previously reported at 3 years for
entire population[5]

For full information on SPRYCEL (dasatinib) please refer to SmPC
at http://www.ema.europa.eu.

About the DASISION Trial

The DASISION trial is a pivotal Phase 3, randomised open-label
study looking at the efficacy and safety of dasatinib versus
imatinibin newly diagnosed, treatment-naïve CP-CML patients. Patients
were randomised to receive treatment with dasatinib 100 mg once-daily
(n=259) or imatinib 400 mg once-daily (n=260).[6] Dasatinib was
superior to imatinib for the primary endpoint of the study, confirmed
complete cytogenetic response (cCCyR) by 12 months (77% vs 66%;
p=0.007).[6] Given the established relationship between achieving
CCyR by 12 months and improved survival rates, longer follow-up may
demonstrate that dasatinib improves long-term outcomes.[6] Three-year
data is now available. Patients will be followed for a planned 5
years.

About SPRYCEL(R)

Discovered and developed by Bristol-Myers Squibb, dasatinib was
initially approved by the FDA and the European Commission in 2006 as
a treatment for adults for all phases of Ph+ CML (chronic,
accelerated, or myeloid or lymphoid blast phase) with resistance or
intolerance to prior therapy including imatinib and Philadelphia
chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL)
intolerant or resistant to prior therapy. In the U.S., dasatinib
received accelerated FDA approval for this indication. Since then,
dasatinib has been approved for this indication in more than 60
countries worldwide.

In 2010, dasatinib 100 mg once daily was approved by the FDA and
European Commission for the treatment of adult patients with newly
diagnosed Ph+ CML in chronic phase. In the U.S., dasatinib received
accelerated FDA approval for this indication. The effectiveness of
dasatinib is based on cytogenetic response and major molecular
response rates. Now, more than 50 countries have approved dasatinib
for this indication.

About Chronic Myeloid Leukemia

CML is a slow-growing type of leukaemia in which the body
produces an uncontrolled number of abnormal white blood cells.[7] CML
accounts for 15% of all leukaemias.[8] The incidence is estimated at
1-2 cases per 100,000.[9]

CML occurs when pieces of two different chromosomes (9 and 22)
break off and attach to each other. The new chromosome is called the
Philadelphia chromosome, which contains an abnormal gene called
BCR-ABL that signals cells to make too many white blood cells. There
is no known cause for the genetic change that causes CML.

Response to treatment can be measured either by Complete
Cytogenetic Response (CCYR) or Major Molecular Response (MMR). CCYR
is the absence of Philadelphia+ chromosomes in a Cytogenetic Testing
made from a bone marrow aspiration. MMR is a 3-log reduction of
BCR-ABL compared to a standardized baseline sample usually measured
in peripheral blood.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines that
help patients prevail over serious diseases.

About Otsuka Pharmaceutical Co., Ltd.

Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global
healthcare company with the corporate philosophy: 'Otsuka-people
creating new products for better health worldwide.' Otsuka
researches, develops, manufactures and markets innovative and
original products, with a focus on pharmaceutical products for the
treatment of diseases and consumer products for the maintenance of
everyday health.

Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of
Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group.
The Otsuka Group has business operations in 23 countries and regions
around the world.

Visit Otsuka Pharmaceutical Co., Ltd. at
http://www.otsuka.co.jp/en.

References: 1. Hochhaus A, et al. Molecular response kinetics and
BCR-ABL reductions in patients with newly diagnosed chronic myeloid
leukemia in chronic phase (CML-CP) receiving dasatinib vs imatinib:
DASISION 3-year follow-up. To be presented at: 17th Congress of the
European Hematology Association (EHA); June 14-17, 2012; Amsterdam,
The Netherlands.

2 Hanfstein B, et al. Early molecular and cytogenetic response is
predictive for long-term progression-free and overall survival in
chronic myeloid leukemia (CML). Leukemia accepted article preview 26
March 2012; doi: 10.1038/leu.2012.85.

3. Marin D, et al. Assessment of BCR-ABL1 transcript levels at 3
months is the only requirement for predicting outcome for patients
with chronic myeloid leukemia treated with tyrosine kinase
inhibitors. J Clin Oncol. 2012;30:232-8.

4. Jabbour E, et al. An exploratory analysis from 3-year DASISION
follow-up examining the impact on patient outcomes of early complete
cytogenetic response at 3 months and major molecular response at 12
months. To be presented at: 17th Congress of the European Hematology
Association (EHA); June 14-17, 2012; Amsterdam, The Netherlands

5. Mayer J, et al. Efficacy and safety of dasatinib vs imatinib
in patients with newly diagnosed chronic myeloid leukemia in chronic
phase (CML-CP): European subpopulation analysis of the phase 3
DASISION trial. To be presented at: 17th Congress of the European
Hematology Association (EHA); June 14-17, 2012; Amsterdam, The
Netherlands.

6. Kantarjian H et al. Dasatinib versus imatinib in newly
diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;
362:2260-2270.

7. Macmillan Cancer Support. Leukaemia Overview.

Available at: http://www.macmillan.org.uk/Cancerinformation/Cance
rtypes/Leukaemia/Leukaemiaoverview.aspx . Last accessed April 2012.

8. National Comprehensive Cancer Network (NCCN). Chronic
Myelogenous Leukemia - Clinical Practice Guidelines in Oncology -
v.1.2007.

9. Baccarani, M. and Dreyling, M. Annals of Oncology.
2010;21:165-167.

UK job codes: 729UK12NP019/ OPUK/0612/SPC/2017, date of
preparation June 2012

Media Contacts
Bristol-Myers Squibb
Astrid Harmel, +33-1-58-83-61-49, astrid.harmel@bms.com
Otsuka Pharmaceutical Europe Ltd.
Ali Ross, +44-7768-337128, aross@otsuka-europe.com

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