Ariad Pharmaceuticals, Inc. has announced additional positive efficacy data on AP23573 its novel mTOR inhibitor from further analysis of its ongoing phase 2 trial of AP23573 in patients with metastatic and/or unresectable bone and soft-tissue sarcomas. The expanded analysis focuses on the 61 patients with an AP23573 clinical benefit response the primary end-point of the 212-patient trial and its relation to progression-free survival.
Patients with an AP23573 clinical-benefit response (CBR) tumour regression or disease stabilization had a progression free survival (PFS) rate at six months of 70 per cent and a median PFS of 36 weeks. The PFS rate in this patient subset was nearly triple that of the overall trial population (vs. 24 per cent), and the median PFS was approximately 21 weeks longer than that of the overall trial population (vs. 15 weeks). These data show that CBR is a clinically useful surrogate for PFS in this difficult-to-treat patient population.
"These results provide further evidence of the beneficial effects of AP23573 in patients with advanced sarcomas and demonstrate that the clinical-benefit responses achieved with AP23573 in this patient population led to clinically meaningful prolongation of progression-free survival," said Harvey J. Berger, M.D., chairman and chief executive officer of Ariad. "We are moving rapidly to launch our randomized, worldwide phase 3 clinical trial of oral AP23573 in patients with advanced sarcomas."
These results are being presented by Dr. Sant Chawla, co-principal investigator of the study, at the 12th annual Connective Tissue Oncology Society (CTOS) meeting in Venice, Italy, November 2 to 4, 2006.
Camille L. Bedrosian, M.D., chief medical officer of Ariad, added, "the data from the expanded analysis of the phase 2 trial further support our phase 3 trial strategy which focuses on advanced sarcoma patients who have experienced a favourable response to prior chemotherapy and have stable disease. We believe this patient population has the greatest likelihood of achieving sustained clinical benefit from treatment with a new molecularly targeted agent such as AP23573."
Earlier this year, at the American Society of Clinical Oncology annual meeting, Ariad announced that AP23573 demonstrated efficacy and was well tolerated as a single agent in this multi-center phase 2 trial of patients with advanced sarcomas, at least 90 per cent of whom had progressive disease. The efficacy of AP23573 was evaluated using two closely related measures of disease progression: CBR (characterized as tumour regression - complete or partial response or disease stabilization for at least four cycles by Recist guidelines), and PFS (reported as the six-month rate and the median duration). The primary end-point of the trial evidenced by CBR rates - was achieved in the three most prevalent types of sarcoma (bone sarcoma, leiomyosarcoma and liposarcoma), and treatment with AP23573 more than doubled PFS when compared to historical control data from the European Organization for Research and Treatment of Cancer (EORTC).
Ariad's lead product candidate, AP23573, is a novel small-molecule inhibitor of the protein mTOR, a "master switch" in cancer cells. Blocking mTOR creates a starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and angiogenesis. AP23573 is currently in phase 1 and 2 clinical trials in patients with solid tumours and hematologic cancers. AP23573 has been designated both as a fast-track product and an orphan drug by the U.S. Food and Drug Administration and as an orphan drug by the European Medicines Agency for the treatment of soft-tissue and bone sarcomas. In addition to its program in oncology, Ariad is collaborating with Medinol Ltd to develop stents and other medical devices that deliver AP23573 to prevent reblockage at sites of vascular injury following stent-assisted angioplasty.