CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jul. 27, 2009--
Pharmaceuticals, Inc. (Nasdaq: ARIA) today announced preliminary
clinical data from an ongoing Phase 1 clinical trial of its
investigational, multi-targeted kinase inhibitor, AP24534,
in patients with advanced hematological cancers. The study results
provide initial clinical evidence of hematologic, cytogenetic and
molecular anti-cancer activity of AP24534 in heavily pretreated patients
with resistant and refractory chronic myeloid leukemia (CML), including
those with the T315I mutant variant of the target protein, Bcr-Abl. An
abstract describing these data is being submitted for presentation at a
major hematology meeting to be held later this year.
Treatment of CML or Philadelphia chromosome positive acute lymphoblastic
leukemia (Ph+ ALL) with Bcr-Abl inhibitors is effective in most patients
but frequently results in the emergence of Bcr-Abl mutations that confer
drug resistance over time. The T315I mutant of Bcr-Abl currently
accounts for approximately 15 to 20 percent of all drug-resistant cases
of CML and Ph+ ALL. First-generation therapies, such as imatinib (Gleevec®),
and second-generation therapies, such as dasatinib (Sprycel®)
and nilotinib (Tasigna®), are not able to inhibit this
mutated protein and, therefore, are not effective against all forms of
CML and Ph+ ALL.
Clinical Proof-of Concept in Patients with CML and Ph+ ALL
Thirty-two patients have been enrolled to date in this trial in six
dosing groups (once daily oral dosing) at five medical centers in the
United States; 28 of the patients have resistant and refractory CML or
Ph+ ALL. All patients have previously been treated with the currently
available first- and second-generation targeted therapies for CML and in
most instances, other investigational agents as well. The patients with
CML and Ph+ALL enrolled in this study only had very limited treatment
options available to them: stem cell transplants, conventional
palliative chemotherapy or investigational agents. The study commenced
patient enrollment in the second quarter of 2008 and will continue
enrolling patients until approximately 50 patients have been enrolled.
Dose-escalation will continue until dose-limiting toxicity is observed.
Key preliminary findings to date include:
In patients with a variety of Bcr-Abl mutations, hematologic
responses, cytogenetic responses, and molecular responses have been
observed with AP24534 treatment. Hematologic and cytogenetic responses
have also been seen in patients with the T315I mutation, which is
resistant to all approved Bcr-Abl inhibitors. Collectively, these data
suggest a significant degree of anti-tumor activity of AP24534 in
highly resistant CML patients.
In addition, of 23 CML patients in the four highest dosing groups, 19
patients remain on study without disease progression, evidence of
control of their disease. Most importantly, of 12 CML patients with
the T315I mutation, nine patients remain on study without disease
progression, providing further evidence of control of their disease.
For many of the patients in the highest dosing groups, the duration of
treatment with AP24534 has been relatively short. In these patients,
it is still early for complete-response assessment. Even in spite of
this, evidence of significant improvement in multiple blood-cell
lineages has been observed.
Preliminary safety assessment shows that AP24534 is well tolerated
without dose-limiting toxicity at doses studied to date. The most
common drug-related adverse events have been thrombocytopenia (low
platelet count) and neutropenia (low white blood cell count), which
the Company believes reflects the underlying disease and the extensive
pre-treatment of the patients in the trial.
To date, pharmacokinetic data indicate that blood levels predicted
preclinically to be associated with complete inhibition of Bcr-Abl
mutations have been surpassed. Pharmacodynamic data show evidence that
AP24534 is acting mechanistically as designed.
“Especially given that we have not yet reached a maximally tolerated
dose, we believe that these preliminary results provide promising
evidence of clinical proof-of-concept of AP24534 in patients with
drug-resistant and refractory CML and Ph+ ALL, including those with the
T315I mutation,” said Frank G. Haluska, M.D., Ph.D., vice president,
clinical affairs at ARIAD.
Dr. Haluska added, “Many of the patients assessed to date have already
had objective evidence of anti-tumor activity – hematologic, cytogenetic
and molecular responses to AP24534. It is important to underscore the
lack of therapeutic options available to the patients included in this
study. We expect to complete enrollment in the study and to undertake
additional evaluation of the safety and efficacy data in the coming
months, leading to a presentation at one of the major hematology
meetings later this year. Pending completion of the trial and evaluation
of the final results, we believe that the results of this trial could
form the basis for a pivotal registration trial of AP24534 starting next
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 more aggressive phases
such as accelerated or blast crisis. Ph+ ALL is a subtype of acute
lymphoblastic leukemia that also carries the Ph+ chromosome that
produces Bcr-Abl. It has a more aggressive course than CML and is often
treated with chemotherapy. Because both of these diseases express the
Bcr-Abl protein, this would render them potentially susceptible to
treatment with AP24534.
ARIAD’s vision is to transform the lives of cancer patients with
breakthrough medicines. The Company’s mission is to discover, develop
and commercialize small-molecule drugs to treat cancer in patients with
the greatest and most urgent unmet medical need – aggressive cancers
where current therapies are inadequate. ARIAD’s lead product candidate,
ridaforolimus, is an investigational mTOR inhibitor in Phase 3 clinical
development in patients with advanced sarcomas and is being developed in
collaboration with Merck & Co., Inc. ARIAD’s second product candidate,
AP24534, is an investigational multi-targeted kinase inhibitor in Phase
1 clinical development in patients with hematological cancers. ARIAD has
an exclusive license to pioneering technology and patents related to
certain NF-κB cell-signaling activity, which may be useful in treating
certain diseases. For additional information about the Company, please
Gleevec® and Tasigna® are registered trademarks of
Novartis AG, and Sprycel® is a registered trademark of
Bristol-Myers Squibb, Inc.
This press release contains “forward-looking statements” including, but
not limited to, statements relating to the preliminary clinical data for
AP24534, continued enrollment in the Phase 1 clinical trial, the
potential for data from this trial forming the basis for a pivotal
registration trial of AP24534 and the timing of the start of such trial.
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.
Maria E. Cantor, 617-621-2208