56 percent major cytogenetic response and 34 percent major
molecular response reported
ATLANTA, & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 9, 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 resistant or refractory chronic myeloid leukemia (CML) or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
The study now shows that 56 percent of chronic-phase CML patients in the
trial, including 70 percent of patients with a T315I mutation, achieved
a major cytogenetic response (MCyR), the primary end-point for
chronic-phase CML patients.
The data are being featured today at 4:30 p.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.
“The 12-month results from the global PACE trial of ponatinib reinforce
its impressive anti-leukemic activity in heavily pretreated CML
patients, regardless of their mutation status or disease stage,” stated
Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia,
The University of Texas M.D. Anderson Cancer Center, Houston, TX.
“Ponatinib demonstrated early responses in chronic-phase patients with
thirty-four percent of these patients achieving a major molecular
response and fifteen percent of those patients achieving a complete
molecular response,” he added. “Of particular importance, responses to
ponatinib appear to be durable, with 91 percent of chronic-phase CML
patients projected to remain in major cytogenetic response at 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 267 patients with chronic-phase CML.
Findings were based on a minimum follow-up of 12 months in
patients remaining on study.
Ninety-three percent of the patients in the trial had received at
least two tyrosine kinase inhibitors prior to enrollment.
Fifty-eight percent of the patients had received three or more
tyrosine kinase inhibitors prior to enrollment.
Chronic-phase patients had bone marrow assessments approximately
every three months for determination of cytogenetic response.
Chronic-phase CML patients evaluable for cytogenetic response
Based on assessment of all evaluable chronic-phase patients in the
trial, 56 percent (149 of 267) of patients achieved a MCyR, with
46 percent achieving a complete cytogenetic response (CCyR). The
median follow up of the chronic-phase CML patients is 15.3 months.
Of the 64 evaluable chronic-phase CML patients with the T315I
mutation, 70 percent (45 of 64) of these patients achieved a MCyR,
with 66 percent achieving a CCyR. The MCyR rate in evaluable
chronic-phase patients without the T315I mutation was 51 percent
(104 of 203).
Thirty-four percent (91 of 267) of chronic-phase CML patients
achieved a major molecular response (MMR).
Fifteen percent (39 of 267) of chronic-phase CML patients achieved
a 4.5-log reduction of BCR-ABL transcripts (MR4.5).
Responses in chronic-phase patients who had received only one
prior TKI (N=19)
There were 19 chronic-phase patients treated with ponatinib in the
PACE trial who had previously received only one tyrosine kinase
inhibitor (TKI). Thirteen of these patients had previously been
treated with imatinib only, and six had previously received either
dasatinib or nilotinib. Of these 19 patients, 84 percent (16 of
19) achieved a MCyR.
Safety profile (N=449)
The most common non-hematologic treatment-emergent adverse events
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