57 percent major hematologic response and median response duration
of 12 months in accelerated-phase CML patients reported
Median overall survival not yet reached in accelerated-phase CML
ATLANTA & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 11, 2012--
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced twelve-month
follow-up data from the pivotal PACE trial of ponatinib,
its investigational BCR-ABL inhibitor, in heavily pretreated patients
with advanced forms of chronic myeloid leukemia (CML) or Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study
now shows that 57 percent of accelerated-phase CML patients in the
trial, including 50 percent of patients with the T315I mutation,
achieved a major hematologic response (MaHR), the primary end-point for
patients with advanced disease in the trial.
The data are being featured today at 8:00 a.m. (ET) in an oral
presentation at the 54th Annual Meeting of the American Society of
Hematology (ASH) being held in Atlanta, Georgia. ARIAD filed for
regulatory approval of ponatinib in the third quarter of 2012 in the
U.S. and in the E.U. based on clinical data from the pivotal PACE trial.
“Patients with advanced forms of Philadelphia chromosome-positive
leukemia and those who have failed currently available therapy have
limited treatment options available to them,” said Hagop M. Kantarjian,
M.D., chairman and professor, Department of Leukemia, University of
Texas M.D. Anderson Cancer Center. “The overall prognosis is poor for
patients with advanced disease.”
“The pivotal PACE trial data show that ponatinib has robust activity in
heavily pretreated patients with accelerated phase CML, more than
doubling their reported best prior responses to available TKI therapy,”
he added. “What is equally striking is that the median time to achieve a
response to ponatinib among accelerated phase patients was only three
weeks and that the median duration of major hematologic response in
these patients is one year.”
Efficacy data were reported at ASH on 444 treated patients in six
pre-specified cohorts at 45 mg of ponatinib administered orally
once daily, including 177 treated patients with advanced disease (i.e.,
accelerated and blast phase CML and Ph+ ALL).
Sixty percent of accelerated phase CML patients and 53 percent of
blast-phase CML and Ph+ ALL patients in the trial had received
three or more tyrosine kinase inhibitors (TKI) prior to enrollment.
Advanced disease patients had a blood test approximately every
month for determination of hematologic response and a bone-marrow
assessment approximately every two months for determination of
Advanced CML and Ph+ ALL patients evaluable for response (N=177)
Fifty-seven percent (47 of 83) of accelerated-phase patients
achieved a MaHR, including 50 percent (9 of 18) of
accelerated-phase patients with the T315I mutation. At study
entry, the reported best prior response of MaHR or better to their
most recent TKI among accelerated-phase patients was 21 percent.
Thirty-four percent (32 of 94) of blast-phase CML or Ph+ ALL
patients achieved a MaHR, including 33 percent (15 of 46) of
blast-phase CML or Ph+ ALL patients with the T315I mutation. At
study entry, the reported best prior response of MaHR or better to
their most recent treatment with a TKI among blast-phase CML or
Ph+ ALL patients was 24 percent.
Thirty-nine percent (32 of 83) of accelerated-phase CML patients
and 31 percent (29 of 94) of blast-phase CML or Ph+ ALL patients
achieved a MCyR. Furthermore, 24 percent (20 of 83) of patients
with accelerated-phase CML and 24 percent (23 of 94) of patients
with blast-phase CML or Ph+ ALL achieved a complete cytogenetic
Median duration, progression-free survival and overall survival
In accelerated-phase CML patients, the median time to achieve a
MaHR was 21 days, and the median duration of this response was 12
months. In blast-phase CML or Ph+ ALL patients, the median time to
achieve a MaHR was 26 days, and the median duration of this
response was 5 months.
Progression-free survival (PFS) in accelerated-phase CML patients
was estimated to be 55 percent at 12 months (median, 18 months).
Progression-free survival in blast-phase CML or Ph+ ALL patients
was estimated to be 15 percent at 12 months (median, 3 months).
Overall survival at 12 months in accelerated-phase CML patients
was estimated to be 84 percent (median not yet reached). Overall
survival at 12 months in blast-phase CML or Ph+ ALL patients was
estimated to be 33 percent, with a median overall survival of 7
Safety profile (N=449)
The most common non-hematologic treatment-emergent adverse events
across all patients in the PACE trial included rash (in 38% of
patients), abdominal pain (38%), headache (35%), dry skin (35%),
and constipation (34%), with the majority of these being grades 1
or 2 in severity.
The most common hematologic treatment-emergent adverse events were
thrombocytopenia (42%), neutropenia (24%), and anemia (20%), which
were primarily grades 3 or 4 in severity.
Pancreatitis and pneumonia were the most common non-hematologic
treatment-emergent serious adverse events (5% each), followed by
abdominal pain (4%), myocardial infarction (3%), congestive heart
failure (3%), atrial fibrillation (3%), and pyrexia (3%). The most
common hematologic serious adverse events were anemia, febrile
neutropenia, and thrombocytopenia (3% each).
Internally discovered at ARIAD, ponatinib is an investigational BCR-ABL
inhibitor that also selectively inhibits certain other tyrosine kinases
in preclinical studies, including FLT3, RET, KIT, and the members of the
FGFR, PDGFR and VEGFR families of kinases.
The primary target for ponatinib is BCR-ABL, an abnormal tyrosine kinase
that is expressed in chronic myeloid leukemia (CML) and
Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Ponatinib was designed using ARIAD’s computational and structure-based
drug design platform to inhibit the activity of BCR-ABL with high
potency and broad specificity. Ponatinib targets not only native BCR-ABL
but also its isoforms that carry mutations that confer resistance to
treatment with existing tyrosine kinase inhibitors, including the T315I
mutation for which no effective therapy currently exists.
About CML and Ph+ ALL
is a cancer of the white blood cells that is diagnosed in approximately
5,000 patients each year in the United States. CML is a type of leukemia
characterized by the increased and unregulated growth of predominantly
myeloid cells in the bone marrow and the accumulation of these cells in
the blood. The genetic hallmark of CML is the Philadelphia chromosome,
an abnormality resulting in a fusion of the BCR and ABL genes. This is
known as Philadelphia chromosome-positive CML, or Ph+ CML.
Treatment of CML usually includes a targeted therapy, a tyrosine kinase
inhibitor (TKI) (e.g., imatinib, dasatinib or nilotinib),
followed by chemotherapy if the disease progresses. Ph+ ALL is a subtype
of acute lymphoblastic leukemia that carries the Ph+ chromosome that
produces the fused BCR-ABL gene. It is known to have a more aggressive
course than CML and is often treated with a combination of chemotherapy
and TKIs. Because both of these diseases express the BCR-ABL protein,
this would render them potentially susceptible to treatment with
ARIAD Pharmaceuticals, Inc. is an emerging global oncology company
focused on the discovery, development and commercialization of medicines
to transform the lives of cancer patients. ARIAD’s approach to
structure-based drug design has led to several internally discovered,
molecularly targeted product candidates for drug-resistant and
difficult-to-treat cancers, including certain forms of chronic myeloid
leukemia and non-small cell lung cancer. For additional information,
This press release contains “forward-looking statements” including, but
not limited to, statements relating to the updated clinical data for
ponatinib, the positive treatment effects of ponatinib over time and the
timing of regulatory filings for marketing approvals. Forward-looking
statements are based on management's expectations and are subject to
certain factors, risks and uncertainties that may cause actual results,
outcome of events, timing and performance to differ materially from
those expressed or implied by such statements. These risks and
uncertainties include, but are not limited to, preclinical data and
early-stage clinical data that may not be replicated in later-stage
clinical studies, the costs associated with our research, development,
manufacturing and other activities, the conduct, timing and results of
pre-clinical and clinical studies of our product candidates, the
adequacy of our capital resources and the availability of additional
funding, and other factors detailed in the Company's public filings with
the U.S. Securities and Exchange Commission. The information contained
in this press release is believed to be current as of the date of
original issue. The Company does not intend to update any of the
forward-looking statements after the date of this document to conform
these statements to actual results or to changes in the Company's
expectations, except as required by law.
Source: ARIAD Pharmaceuticals, Inc.
ARIAD Pharmaceuticals, Inc.
Liza Heapes, 617-621-2315