ARIAD announces oral ridaforolimus achieved primary endpoint of improved progression free survival in patients with metastatic soft-tissue or bone sarcomas in the phase III succeed trial.
ARIAD Pharmaceuticals Inc. announced top-line data showing that ridaforolimus, an investigational oral mTOR inhibitor, met the primary endpoint of improved progression-free survival (PFS) compared to placebo in the Phase 3 SUCCEED trial conducted in patients with metastatic soft-tissue or bone sarcomas who previously had a favourable response to chemotherapy. Merck is currently developing ridaforolimus in multiple cancer indications under an exclusive license and collaboration agreement with ARIAD. Complete findings from the SUCCEED trial will be submitted for presentation at an upcoming medical meeting this year.
Based on the full analysis of 552 PFS events in 711 patients, determined by an independent review committee, the blinded prospective study achieved its primary endpoint, with a statistically significant (p=0.0001) 28 percent reduction by ridaforolimus in the risk of progression compared to placebo (hazard ratio=0.72). Determination of median PFS for each arm of the trial demonstrated that ridaforolimus treatment resulted in a statistically significant 21 percent (3.1 week) improvement in median PFS (ridaforolimus, 17.7 weeks vs. placebo, 14.6 weeks).
Based on the full analysis of PFS determined by the investigative sites, there also was a statistically significant (p0.0001) 31 percent reduction by ridaforolimus in the risk of progression compared to placebo (hazard ratio=0.69). Ridaforolimus treatment resulted in a statistically significant 52 percent (7.7 week) improvement in median PFS (ridaforolimus, 22.4 weeks vs. placebo, 14.7 weeks).
The most common side effects observed in the study to date were consistent with the known safety profile of ridaforolimus and included stomatitis (e.g., mouth sores), fatigue, diarrhea and thrombocytopenia.
This trial remains active, and study participants continue to be followed to gather additional data on secondary endpoints, including overall survival and the safety profile of ridaforolimus. Merck currently plans to file for marketing approval of oral ridaforolimus in 2011, subject to final collection and analysis of all available data from the trial.
“Patients with metastatic soft-tissue and bone sarcomas have extremely limited treatment options available to them,” stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. “These top-line data illustrate how devastating metastatic sarcomas can be, even in patients who have responded favourably to conventional chemotherapy. We are very pleased with the positive outcome of the SUCCEED trial and the statistically significant improvement in progression-free survival in those patients treated with oral ridaforolimus.”
About the SUCCEED Trial
The SUCCEED trial is a randomized (1:1), placebo-controlled, double-blind study of oral ridaforolimus administered at 40 mg/day (five of seven days/week) in patients with metastatic soft-tissue or bone sarcomas who demonstrated a favourable response to prior conventional chemotherapy. Oral ridaforolimus was granted a Special Protocol Assessment (SPA) by the U.S. Food and Drug Administration (FDA) for the SUCCEED trial. The European Medicines Agency (EMA) has also provided protocol advice regarding the trial design as part of its Protocol Assistance program. More information about this trial can be found at www.clinicaltrials.gov NCT00538239
Ridaforolimus is an investigational targeted and potent small-molecule inhibitor of the protein mTOR, a protein that acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival, integrating signals from proteins, such as PI3K, AKT and PTEN, known to be important to malignancy.