|ARIAD Announces Initiation of Randomized Phase 3 Trial of Ponatinib in Newly Diagnosed Patients with Chronic Myeloid Leukemia|
“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
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
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 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
For more information about the EPIC trial, patients and physicians should visit http://clinicaltrials.gov/ct2/show/NCT01650805?term=ponatinib&rank=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.
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
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.
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