CAMBRIDGE, Mass.–(BUSINESS WIRE)–
ARIAD
Pharmaceuticals, Inc. (ARIA) today announced the initiation
of the randomized Phase 3 trial of ponatinib,
its investigational pan-BCR-ABL inhibitor, in adult patients with newly
diagnosed chronic myeloid leukemia (CML). The EPIC (Evaluation
of Ponatinib versus Imatinib in Chronic Myeloid
Leukemia) trial is designed to provide definitive clinical data to
support regulatory approval of ponatinib in treatment-naïve CML
patients. The efficacy of ponatinib will be assessed in comparison to
imatinib based on evaluation of the primary endpoint of major molecular
response (MMR) rate at 12 months. ARIAD expects to complete patient
enrollment in the trial by the end of 2013.
“The start of the EPIC trial represents an important milestone in the
development of ponatinib in CML and builds on the strong clinical data
that we have obtained to date in patients with more advanced disease. We
have designed the EPIC trial with comprehensive and well-aligned input
from key opinion leaders and regulatory authorities in the United
States, Europe and Japan and anticipate strong interest from
investigators and their patients,” stated Harvey
J. Berger, M.D., chairman and chief executive officer of ARIAD.
Dr. Berger added, “The treatment of newly diagnosed CML patients has
shifted in recent years to the use of second-generation BCR-ABL
inhibitors. The EPIC trial will evaluate whether ponatinib – a
pan-BCR-ABL inhibitor – produces anti-leukemic responses in these newly
diagnosed patients and potentially prevents the emergence of resistance
mutations seen with other tyrosine kinase inhibitors.”
Trial Design and Statistical Analysis
The EPIC trial is a randomized, two-arm, multicenter trial that compares
the efficacy of ponatinib with that of imatinib in adult patients with
newly diagnosed CML in the chronic phase. The trial will be conducted at
up to 175 investigational sites in North America, Europe and
Asia-Pacific. Patients in the trial must be at least 18 years of age and
diagnosed with CML within six months prior to enrollment. Approximately
500 patients will be randomized 1:1 to standard doses of ponatinib (45
mg given orally once daily) or imatinib (400 mg given orally once
daily). Escalation of the imatinib dose to 600 mg or 800 mg per day is
permitted.
The MMR rate at 12 months of treatment is the primary endpoint of the
trial. This endpoint was chosen to support accelerated approval in the
United States. All patients will be evaluated for molecular response
(MR) using quantitative reverse transcriptase polymerase chain reaction
(qRT PCR) at a single central laboratory (Molecular MD, Portland, OR).
MMR is defined as a less than or equal to 0.1% ratio of BCR-ABL to ABL
transcripts on the International Scale measured in peripheral blood.
The EPIC trial was designed to have a 90% power to detect a 15% absolute
improvement in 12-month MMR rate by ponatinib compared to imatinib. This
was based, in part, on the results of the nilotinib (ENESTnd) and
dasatinib (DASISION) Phase 3 trials. The 12-month MMR rates for the
imatinib arms in these two trials were 22% and 28%, respectively. Using
the more conservative estimate of the 12-month MMR rate for imatinib,
the upper bound of the 95th percentile confidence interval
for the higher of these two estimates is 34%. The ENESTnd trial was
designed to demonstrate a 15% absolute improvement in 12-month MMR rate
comparing nilotinib to imatinib. Thus, the EPIC trial is 90% powered to
detect a 15% absolute improvement in 12-month MMR rate by ponatinib
compared to imatinib (i.e., 49% vs. 34%).
Key secondary endpoints include: MMR at five years, MR at three months
(a reduction in the level of BCR-ABL transcripts to 10% or less),
complete cytogenetic response rate at 12 months, progression-free
survival and overall survival. Each patient will be followed for up to
eight years from the time the last patient is randomized to either
treatment arm.
A key design feature of the trial is an interim analysis of efficacy.
This analysis will take place 12 months after half of the patients in
the trial have been randomized. The interim analysis will focus on the
primary endpoint of the MMR rate at 12 months of treatment and,
depending on the results, may allow ARIAD to file for regulatory
approval of ponatinib in the newly diagnosed clinical setting
approximately six months earlier than otherwise.
“The timing of the interim analysis will be based on the rate of patient
enrollment in the trial,” stated Frank G. Haluska, M.D., Ph.D., chief
medical officer at ARIAD. “The EPIC trial is powered to show the same
absolute improvement in 12-month MMR rate as was seen with nilotinib in
its similar trial that employed this endpoint.”
For more information about the EPIC trial, patients and physicians
should visit http://clinicaltrials.gov/ct2/show/NCT01650805?term=ponatinibrank=7,
call the U.S. toll-free number 1-877-621-2302 or the international
number 1-617-621-2302, or e-mail inquiries to EPICtrialdesk@ariad.com.
About Ponatinib
Internally discovered at ARIAD, ponatinib is an investigational
pan-BCR-ABL inhibitor that also selectively inhibits certain other
tyrosine kinases in preclinical studies, including FLT3, RET, KIT, FGF
and PDGF receptors.
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 very 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 exists. ARIAD expects to file for initial
approval of ponatinib in patients with resistant or intolerant CML and
Ph+ ALL in the third quarter of 2012.
About CML and Ph+ ALL
CML
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 the more aggressive
phases referred to as accelerated phase 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.
About ARIAD
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 or
difficult-to-treat cancers, including certain forms of chronic myeloid
leukemia and non-small cell lung cancer. For additional information,
visit http://www.ariad.com
or follow ARIAD on Twitter
(@ARIADPharm).
This press release contains “forward-looking statements” including, but
not limited to, statements relating to the potential that ponatinib is
an effective treatment for newly diagnosed patients with chronic-phase
CML when compared with standard imatinib and the timing of filing for
regulatory approval of ponatinib in the newly diagnosed clinical
setting. 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.
Article source: http://finance.yahoo.com/news/ariad-announces-initiation-randomized-phase-113500866.html