AG3340 Exhibits Marked Anti-Tumor Activity in Preclinical Models
LA JOLLA, Calif., June 17 /PRNewswire/ -- Agouron Pharmaceuticals, Inc.
(Nasdaq: AGPH) today released encouraging results from two phase I studies and
one preclinical study of its oral anti-angiogenesis drug, AG3340. The data
were reported today at the 10th European Organization for Research and
Treatment of Cancer (EORTC) meeting in Amsterdam, the Netherlands.
Phase I studies in advanced cancer patients
In a phase I safety and tolerability study of AG3340 administered orally
twice daily (BID) in patients with advanced cancer, including lung, prostate,
kidney, and colorectal cancers as well as sarcoma and melanoma, disease was
stabilized in more than 25% of 47 evaluable patients who were treated for
periods of 16 to 40 weeks. Either two or three patients in each of five small
dosing groups (5mg, 10mg, 25mg, 50mg and 100mg BID) comprising the 47 patients
experienced stable disease. Three patients (one each with non-small cell lung
cancer, renal carcinoma, and melanoma) were found to have minor reductions in
tumor volume. Nine other evaluable patients in two additional dosing groups
(1mg and 2mg BID) had not yet received 16 weeks of treatment and are still
under evaluation. AG3340 was found to be generally well tolerated in this
study. Expected musculoskeletal side effects, including arthralgias and body
aches, occurred less frequently at doses below 25mg BID and were managed
effectively by a rest from treatment followed by a dose reduction.
Based on the safety and tolerability data from this study, pivotal phase
II/III clinical trials have been initiated using AG3340 in 5mg, 10mg, and l5mg
doses given BID in combination with standard chemotherapy in patients with
advanced non-small cell lung cancer or advanced hormone-refractory prostate
cancer.
AG3340 is well tolerated in combination in advanced prostate cancer study
A separate phase I study found that AG3340 in combination with
chemotherapy was generally well tolerated among patients with advanced
prostate cancer who were resistant to hormonal therapies. This study
evaluated the use of AG3340 -- in a dose of 25 mg BID -- in combination with
Novantrone(R) (mitoxantrone) plus prednisone in 15 patients with advanced
prostate cancer. In this ongoing study, nine patients have received the
combination treatment for more than ten weeks; seven patients have received
treatment for more than 18 weeks.
Pharmacokinetic analysis of the available data confirmed that AG3340 blood
levels are not affected by administration with mitoxantrone. No unexpected
side effects occurred in the patients in this study.
AG3340 inhibits tumor growth in preclinical study
In a separate preclinical study, AG3340 was found to be a potent inhibitor
of the growth of chemotherapy-resistant human non-small cell lung cancer
tumors in mice. Here, administration of AG3340 resulted in a
dose-dependent decrease in tumor growth by up to 65% as compared to controls.
Paraplatin(R) (carboplatin), a currently available chemotherapeutic agent,
demonstrated a similar amount of anti-tumor effect at toxic doses, whereas
AG3340 inhibited growth at well-tolerated doses. The study also demonstrated
that the combination of carboplatin and AG3340 was more effective than either
agent alone, suggesting that the combination of the two drugs could provide
beneficial clinical results.
A key action of AG3340 was also demonstrated by finding a 77% reduction in
the formation of new tumor-associated blood vessels. Neovascularization, or
new blood vessel formation (angiogenesis), is required to support growing
tumors. In animal studies, AG3340 exerts anti-angiogenic effects, halting the
formation of new blood vessels, and thereby starving tumor cells.
AG3340 is an orally active, synthetic molecule designed to inhibit the
growth, invasion and metastasis of solid tumors by inactivating certain
members of a family of enzymes known as matrix metalloproteases (MMPs).
AG3340 selectively inhibits those MMPs believed to be involved in tumor
progression. A primary goal of the clinical studies of AG3340 is to determine
whether this distinctive selectivity results in a favorable clinical profile
of safety and efficacy. Agouron is also conducting preclinical evaluations of
third-generation MMP inhibitors with selectivity profiles distinct from that
of AG3340.
For patient and physician information on AG3340 clinical trials in non-
small cell lung and hormone refractory prostate cancer, dial
toll-free 1-888-9-CANCER.
Agouron Pharmaceuticals, Inc. is an integrated pharmaceutical company
committed to the discovery, development, manufacturing, and marketing of
innovative therapeutic products engineered to inactivate proteins that play
key roles in cancer, AIDS, and other serious diseases.
This press release may contain forward-looking statements or predictions.
These statements represent the Company's judgment as of this date and are
subject to risks and uncertainties (including those associated with regulatory
approvals and the impact of competitive products) that could cause the actual
results to differ materially. Important factors concerning these risks are
discussed in the Company's Form 10-K for the fiscal year ended June 30, 1997
currently on file with the Securities and Exchange Commission. Agouron
undertakes no obligation to publicly release the result of any revisions to
such forward-looking statements which may be made to reflect events or
circumstances after the date hereof or to reflect the occurrence of
unanticipated events.
For more information on Agouron, you may visit the Agouron Web Site at
http://www.agouron.com.
Paraplatin(R) is a registered trademark of Bristol-Myers Squibb
Oncology/Immunology. Novantrone(R) is a registered trademark of the Immunex
Corporation.
SOURCE Agouron Pharmaceuticals, Inc.
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Head of Corporate Communications, 619-622-3009, or Media: Joy
Schmitt, Manager Product Public Relations, 619-622-3220, both of
Agouron Pharmaceuticals
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