Introgen Therapeutics, Inc. has initiated the efficacy analyses of its Advexin phase III study. The efficacy evaluation of the study will incorporate the prospective analyses of patients defined by clinical and molecular prognostic biomarkers, including abnormal p53 protein levels. Abnormality of the p53 tumour suppressor is one of the most common and fundamental molecular defects in cancer.
The phase III study compares Advexin p53 therapy versus methotrexate in patients with recurrent head and neck cancer. The prospective efficacy assessment of the randomised, controlled clinical trial is based upon analyses of prognostic biomarkers and clinical outcome.
The phase III statistical analysis plan was finalized in conjunction with the US Food and Drug Administration (FDA) and incorporated into Introgen's Investigational New Drug application. Introgen announced that it has received permission from FDA to accelerate the phase III0 safety analyses and to perform efficacy analyses for this study. In 2006, review by an independent Data Safety Monitoring Board noted no safety issues with the phase III study. The phase III efficacy analyses will utilize prospective, blinded prognostic biomarker testing of samples by an independent laboratory and will utilize a response confirmation board and statistical controls in the analyses process.
Max W. Talbott, Ph.D., Introgen's senior vice president of worldwide commercial development and regulatory affairs said, "Our initiation today of these new efficacy analyses is another milestone in our Advexin registration process. We expect to conclude the analyses and make pending marketing authorization applications during 2007. This will include our head and neck cancer filings in the US and Europe and our Li-Fraumeni Syndrome application in the European Union."
Advexin's mechanism of action is targeted to restoring p53 tumour suppressor function and the detection of abnormal p53 is a logical prognostic biomarker for Advexin efficacy. Analyses of prognostic biomarker defined patients in phase II Advexin clinical trials showed high statistical correlation with survival and tumour response in recurrent head and neck cancer patients.
The endpoints of the phase III study are tumour response and survival including evaluation of prognostic biomarker defined populations. Introgen has determined that there is sufficient enrolment in this study to provide for definitive determination of Advexin's efficacy in the recurrent head and neck patient population. These analyses will also evaluate comparative toxicity of methotrexate and Advexin. Methotrexate is a commonly utilized chemotherapy for the treatment of cancer.