ARIAD REPORTS TUMOR REGRESSION WITH AP23573 AS A SINGLE AGENT
IN PATIENTS WITH RELAPSED AND/OR REFRACTORY CANCER
Updated Phase 1 Clinical Results on Novel mTOR Inhibitor Presented at
International Cancer Symposium
Cambridge, MA, September 30, 2004 – ARIAD Pharmaceuticals, Inc. (Nasdaq:
ARIA) today
announced, for the first time, updated results of two Phase 1 clinical
trials of its novel mTOR
inhibitor, AP23573 as a single agent, showing documented tumor
regression in patients with
advanced cancers – most of whom had progressive disease upon entering
the trial and
virtually all of whom had failed alternative treatments. These clinical
results are being
presented today at the 2004 EORTC-NCI-AACR Symposium on Molecular
Targets and
Cancer Therapeutics in Geneva, Switzerland.
Combined Trial Results: Anti-tumor Responses
Of 49 evaluable patients in the two trials, tumor regression was
demonstrated in 9 patients (4
“partial responses” by RECIST with at least 30% reduction in tumor size
and 5 “minor
responses” with 15% to 29% reduction). In an additional 15 patients,
disease stabilization
was achieved. Overall, 49% (24 of 49) of the patients in the two trials
had documented antitumor
responses (including partial and minor responses and stable disease),
with a median
response of 5 months in those demonstrating anti-tumor responses,
extending to greater than
18 months – the longest treatment to date.
Anti-tumor responses were demonstrated in 9 different refractory and/or
relapsed cancers,
including all evaluable patients with sarcoma (5 of 5), kidney cancer (7
of 7) and lymphoma (1
of 1), as well as 2 of 3 patients with non-small cell lung (NSCL) cancer.
“We are extremely encouraged by the number of patients with relapsed
and/or refractory
cancer who demonstrated tumor regression with AP23573 in Phase 1
clinical trials, as well as
the breadth of tumors that are responding to our novel mTOR inhibitor,”
said Harvey J. Berger,
M.D., chairman and chief executive officer of ARIAD. “As a clinician, I
was particularly
struck by the results in one patient with a Ewing’s sarcoma who had
received nine prior
anticancer regimens. After four cycles of AP23573, CT scans showed a 62%
reduction in the
size of the mass; this patient continues on study. Phase 2 studies of
AP23573 are ongoing in
patients with hematologic cancers and solid tumors.”
Daily Dosing Trial Results
In the 27 evaluable patients in the daily dosing trial – the dosing
regimen being used in
current Phase 2 clinical trials – AP23573 produced tumor regression in 7
patients:
• Partial response – Sarcoma, lymphoma, and NSCL cancer (1 each)
• Minor response – Sarcoma, NSCL, kidney, and thyroid cancers (1 each).
An additional 9 patients in this trial had stabilization of their
disease (overall 59% with
anti-tumor response).
Weekly Dosing Trial Results
In the 22 evaluable patients in the weekly dosing trial, AP23573 also
produced tumor
regression in 2 patients, both with particularly difficult-to-treat
cancers, even when the drug
was administered only once each week:
• Partial response – Bladder cancer (1) (unconfirmed, repeat scans pending)
• Minor response – Mesothelioma, a form of chest-cavity cancer (1).
An additional 6 patients in this trial had stabilization of their
disease (overall 36% with antitumor
response).
Additional Combined Trial Results
The daily dosing trial is ongoing at the Institute for Drug Development,
Cancer Therapy and
Research Center, San Antonio (M. Mita, M.D. and A. Tolcher, M.D.), and
the weekly dosing
trial is ongoing at the University of Chicago Cancer Center (A. Desai,
M.D. and M. Ratain,
M.D.).
AP23573 has been well tolerated by patients in both trials, with
generally mild or moderate,
readily reversible adverse events. The dose-limiting toxicity was severe
oral mucositis, an
inflammatory irritation of the mucous membranes of the mouth and a
common finding in
cancer patients on various types of treatments.
Pharmacodynamic assays on patient samples demonstrated a good
correlation of blood levels
of AP23573 with inhibition of AP23573’s molecular target, the protein
mTOR. Greater than
90% inhibition was observed within 1 hour after dosing in all patients
in both trials. With
daily dosing of AP23573, there was sustained inhibition of mTOR activity
for up to 10 days in
the majority of patients studied.
The pharmacokinetic (blood-clearance) profile of AP23573 was found to be
highly predictable
and reproducible, with a median half-life of 49 hours for all patients
with complete data in the
two trials. In contrast to other mTOR inhibitors in clinical trials,
AP23573 was stable in vivo
and is not a pro-drug.
About AP23573
The small-molecule drug, AP23573, starves cancer cells and shrinks
tumors by inhibiting the
critical cell-signaling protein, mTOR, which regulates the response of
tumor cells to nutrients
and growth factors, and controls tumor blood supply and angiogenesis
through effects on
Vascular Endothelial Growth Factor (VEGF).
About the Company
ARIAD is engaged in the discovery and development of breakthrough
medicines to treat cancer
by regulating cell signaling with small molecules. The Company is
developing a comprehensive
approach to patients with cancer that addresses the greatest medical
need – aggressive and
advanced-stage cancers for which current treatments are inadequate.
ARIAD also has an
exclusive license to pioneering technology and patents related to
certain NF-κB treatment
methods, and the discovery and development of drugs to regulate NF-κB
cell-signaling activity,
which may be useful in treating certain diseases. Additional information
about ARIAD can be
found on the web at http://www.ariad.com.
Some of the matters discussed herein are “forward-looking statements”
within the meaning of the
Private Securities Litigation Reform Act of 1995. Such statements are
identified by the use of words
such as “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,”
“believe,” and other words and
terms of similar meaning in connection with any discussion of future
operating or financial
performance. Such statements are based on management’s current
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
forward-looking statements.
These risks include, but are not limited to, risks and uncertainties
regarding the Company’s ability to
accurately estimate the actual research and development expenses and
other costs associated with the
preclinical and clinical development of our product candidates, the
adequacy of our capital resources
and the availability of additional funding, risks and uncertainties
regarding the Company’s ability
to successfully conduct preclinical and clinical studies of its product
candidates, risks and uncertainties
that clinical trial results, such as those noted in this press release,
at any phase of development may
be adverse or may not be predictive of future result or lead to
regulatory approval of any of the
Company’s product candidates, and risks and uncertainties relating to
regulatory oversight,
intellectual property claims, the timing, scope, cost and outcome of
legal proceedings, future capital
needs, key employees, dependence on the Company’s collaborators and
manufacturers, markets,
economic conditions, products, services, prices, reimbursement rates,
competition and other risks
detailed in the Company’s public filings with the Securities and
Exchange Commission, including
ARIAD’s Annual Report on Form 10-K for the fiscal year ended December
31, 2003. The information
contained in this document 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.
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CONTACT: Tom Pearson
(610) 407-9260
Kelly Lindenboom
(617) 621-2345
