~ Robust anti-leukemic activity in CML patients who have become
resistant or intolerant to available tyrosine kinase inhibitors
~ 54 percent major cytogenetic response and 30 percent major
molecular response reported in heavily pretreated chronic-phase CML
~ Investor meeting and webcast to be held today at 12:00 p.m. (CT)
CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 4, 2012--
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated
clinical data from the pivotal PACE trial of its investigational
pan-BCR-ABL inhibitor, ponatinib,
in patients with chronic myeloid leukemia (CML) or Philadelphia-positive
acute lymphoblastic leukemia (Ph+ ALL), who are resistant or intolerant
to dasatinib or nilotinib or who have the T315I mutation. These data
show that 54 percent of chronic-phase CML patients in the trial,
including 70 percent of patients who have a T315I mutation, achieved a
major cytogenetic response. ARIAD expects to file for regulatory
approval of ponatinib in the U.S. and the EU in the third quarter of
2012 based on these clinical data.
The PACE trial data are being featured today at 9:00 a.m. (CT) in an
oral presentation at the 2012 American Society of Clinical Oncology
(ASCO) annual meeting taking place in Chicago, IL.
“The findings from the global PACE trial of ponatinib confirm its
impressive anti-leukemic activity in patients with CML at all stages who
are resistant or intolerant to dasatinib or nilotinib, or who have the
T315I mutation for which there are no currently available treatments,”
stated Jorge Cortes, M.D., professor and deputy chair, Department of
Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston,
“Clinical responses to ponatinib were observed in patients regardless of
their mutation status or disease stage,” he added. “Of particular
importance, responses to ponatinib appear to be durable, with 93 percent
of chronic-phase CML patients projected to remain in major cytogenetic
response at one year, clearly highlighting the potency of ponatinib.”
Updated Results Presented at ASCO
Efficacy data were reported at ASCO on 444 treated patients in six
pre-specified cohorts at 45 mg of ponatinib administered orally
Patients were assigned to a cohort based on their phase of disease
(chronic-phase, accelerated-phase or blast-phase CML/Ph+ALL) and
T315I mutation status (with or without the mutation).
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.
Findings on each of the 444 patients treated in the study were
based on at least six months of available response data.
The T315I mutation status was determined using a standardized
Sanger sequencing test by MolecularMD in Portland, OR.
Chronic-phase CML patients evaluable for cytogenetic response
Based on assessment of all evaluable chronic-phase patients in the
trial, 54% (144 of 267) achieved a major cytogenetic response
(MCyR), with 44% achieving a complete cytogenetic response (CCyR).
The median follow up of the chronic-phase CML patients is 10.1
months. MCyR is the primary end-point for chronic-phase CML
patients in this pivotal trial of ponatinib.
Of the 64 evaluable chronic-phase CML patients with the T315I
mutation, 70% (45 of 64) of these patients achieved a MCyR, with
66% achieving a CCyR. The MCyR rate in evaluable chronic-phase
patients without the T315I mutation was 49% (99 of 203).
Thirty percent (79 of 267) of chronic-phase patients achieved a
major molecular response (MMR). Of 64 chronic-phase patients with
the T315I mutation, 50% (32 of 64) attained a MMR. MMR is the
primary end-point in ARIAD’s planned Phase 3 trial of ponatinib
against imatinib in newly diagnosed CML patients that is expected
to begin in the 3Q of 2012.
Responses in chronic-phase patients who had received only one
prior TKI (N=21)
There were a total of 21 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 eight had
previously received either dasatinib or nilotinib. Of the 21
patients who received ponatinib following treatment with only one
prior TKI, 86 percent (18/21) achieved a MCyR.
Advanced phase CML patients evaluable for response (N=177)
Sixty percent (39 of 65) of accelerated-phase patients in the
resistant or intolerant cohort achieved a major hematologic
response (MaHR). Fifty percent (9 of 18) of accelerated-phase
patients with the T315I mutation achieved a MaHR. MaHR is the
primary end-point in accelerated and blast-phase CML or Ph+ALL
patients in the trial.
Thirty-five percent (17 of 48) of blast-phase CML or Ph+ALL
patients in the resistant or intolerant group achieved a MaHR.
Similarly, 33% percent (15 of 46) of blast-phase CML or Ph+ALL
patients with the T315I mutation also had a MaHR.
Thirty-four percent (22 of 65) of accelerated phase patients and
27% (13 of 48) of blast phase or Ph+ALL patients in the resistant
or intolerant cohorts achieved a MCyR. Twenty percent (13 of 65)
of patients in accelerated phase and 23 percent (11 of 48) of
patients in blast phase or Ph+ALL in this same group achieved a
Safety profile (N=449)
Updated safety data show ponatinib to have a favorable profile in
these heavily pretreated patients.
The most common adverse events considered related to ponatinib
included thrombocytopenia (in 35% of patients), rash (32%), dry
skin (30%), abdominal pain (22%), and headache (18%). Elevated
serum lipase, fatigue and arthralgia were observed less frequently.
The incidence of pancreatitis across the study and including all
grades was 6%. Pancreatitis was previously determined to be the
dose-limiting toxicity of ponatinib in the Phase 1 trial.
“These updated findings of the PACE trial show beneficial responses and
an increasing molecular response rate to ponatinib,” said Frank G.
Haluska, M.D., Ph.D., senior vice president and chief medical officer of
ARIAD. “Importantly, these data provide clear evidence of a favorable
safety and tolerability profile of ponatinib in resistant or intolerant
CML patients. The adverse event profile is similar to what was seen in
the earlier Phase 1 study of ponatinib, although the incidence of
pancreatitis is less in the PACE trial,” added Dr. Haluska.
Investor Meeting Today at 12:00 p.m. (CT)
ARIAD will hold an investor meeting and webcast at 12:00 p.m. (CT)/1:00
p.m. (ET) today, Monday, June 4, 2012 to review these data being
presented at ASCO. The event will feature Jorge Cortes, M.D., professor
and deputy chair, Department of Leukemia, The University of Texas M.D.
Anderson Cancer Center. This event is being held at the Chicago Hilton
Hotel for ARIAD’s research analysts and for institutional investors
attending the ASCO conference and will be webcast live on the investor
relations page of the Company's website at http://investor.ariad.com.
A replay of this investor event will be available on the ARIAD
website approximately three hours after the presentation and will be
archived for four weeks. To ensure a timely connection to the live
webcast, participants should log onto the webcast at least fifteen
minutes prior to the scheduled start time.
About CML and Ph+ ALL
is characterized by an excessive and unregulated production of white
blood cells by the bone marrow due to a genetic abnormality that
produces the BCR-ABL protein. After a chronic phase of production of too
many white blood cells, CML typically evolves to more aggressive phases
such as accelerated or blast crisis. Ph+ ALL is a subtype of acute
lymphoblastic leukemia that carries the Ph+ chromosome that produces
BCR-ABL. It has a more aggressive course than CML and is often treated
with a combination of chemotherapy and tyrosine kinase inhibitors.
Because both of these diseases express the BCR-ABL protein, this would
render them potentially susceptible to treatment with ponatinib.
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 three internally discovered,
molecularly targeted product candidates for drug-resistant and
difficult-to-treat cancers, including certain forms of chronic myeloid
leukemia, soft tissue and bone sarcomas and non-small cell lung cancer.
For additional information, visit http://www.ariad.com.
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.
Lynn Granito, 212-253-8881