Abnormality of the p53 tumor suppressor is one of the most common and fundamental molecular defects in cancer. ADVEXIN's mechanism of action is targeted to restoring p53 tumor suppressor function and the detection of abnormal p53 is a logical predictive biomarker for ADVEXIN efficacy. In a study of 28 recurrent head and neck cancer patients in Phase 2 clinical trials, abnormal p53 was shown to correlate with increased survival and tumor responses following ADVEXIN treatment.
The median survival of patients with tumors expressing the abnormal p53 biomarker was 11.6 months compared to only 3.5 months in patients whose tumors had normal p53. The association between the abnormal p53 biomarker and increased survival following ADVEXIN therapy was highly statistically significant (p=0.0007).
The abnormal p53 biomarker was also associated with a statistically significant increase in tumor responses to ADVEXIN therapy. A reduction in tumor size was observed in 40 percent of patients with the abnormal p53 biomarker compared to none (zero percent) of patients with p53 normal tumors. In addition, tumor growth control lasting for a minimum of two treatment cycles was observed in 75 percent of patients with abnormal p53 tumors compared to 27 percent of patients with a normal p53 biomarker. Both the increased reduction in tumor size and tumor growth control associated with the abnormal p53 biomarker were statistically significant (p=0.02).
Importantly, patients with abnormal p53 tumors are known to have poor responses and survival following standard treatments. These patients have the greatest need for new therapies and they achieved the most benefit from ADVEXIN t reatment.
"The rationale for targeted therapies is to match specific treatments with the underlying molecular abnormalities of a patient's cancer," said Robert E. Sobol, M.D., senior vice president, Medical and Scientific Affairs at Introgen. "The abnormal p53 biomarker identifies patients most likely to benefit from ADVEXIN therapy who are known to do poorly with conventional treatment. We believe that these biomarker data will support the regulatory approval of ADVEXIN and improve the care of patients with abnormal p53 tumors."
These biomarker analyses were conducted with pre-treatment samples on a completely blinded basis by an independent laboratory that was not aware of the clinical results of the study. The test utilized to detect the p53 biomarker was performed under good laboratory practice procedures and is of the same type employed to detect the abnormal biomarker that guides the use of Herceptin(R) (Trastuzumab), another cancer biological therapy that applied a biomarker to obtain regulatory approval.
Introgen has officially amended its Phase 3 statistical analysis plan and Investigational New Drug Application with the U.S. Food and Drug Administration to incorporate the use of the p53 biomarker to support licensure of ADVEXIN.
Also at the conference, data was presented regarding Introgen's other Phase 3 product, INGN 241, indicating that inhibitors of a class of stress proteins called heat shock proteins enhances INGN 241-mediated tumor cell death. These pre-clinical data provide insight into INGN 241 mechanisms of action and identify future strategies to enhance its activity.
Biomarkers are tests or measurements that predict response to treatment. Molecular biomarkers include measurements of genetic markers or molecular pathways while clinical biomarkers refer to clinical history or clinical measurements. Introgen's molecular biomarkers include the identification of aberrant p53 function by a ro utine assay performed by pathology laboratories worldwide detecting abnormally elevated levels of p53 protein in tumor tissues. Introgen believes that application of molecular and clinical biomarkers can predict the patients who are most likely to respond to ADVEXIN treatment.
ADVEXIN p53 therapy is a targeted molecular therapy with broad applicability in a wide range of tumor types and clinical settings because it targets one of the most fundamental and common molecular defects, abnormal p53 tumor suppressor function, associated with cancer initiation, progression and treatment resistance. ADVEXIN has demonstrated increased survival and tumor growth control in recurrent head and neck cancer patients. ADVEXIN has demonstrated clinical activity in a number of solid tumor types in multiple phase 1, 2 and 3 clinical trials conducted worldwide.
About INGN 241
INGN 241 is being tested in a Phase 2 clinical trial for patients suffering from advanced melanoma and in a Phase 3 clinical trial in combination with radiation therapy in solid tumors. The mda-7 gene is the active component of INGN 241 and was discovered in the laboratory of Dr. Paul B. Fisher, professor of clinical pathology at Columbia University. Introgen holds an exclusive worldwide sublicense to the Columbia University rights for all gene therapy applications from GlaxoSmithKline.
Introgen Therapeutics, Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted molecular therapies for the treatment of cancer and other diseases. Introgen is developing molecular therapeutics, immunotherapies, vaccines and nano-particle tumor suppressor therapies to treat a wide range of cancers using tumor suppressors, cytokines and genes. Introgen maintains integrated research, development, manufacturing, clinical and regulatory departments and operates multiple manufacturing facilities including a commercial scale cGMP manufacturing facility.
Statements in this release that are not strictly historical may be "forward-looking" statements, including those relating to Introgen's future success with its ADVEXIN and INGN 241 clinical development programs for treatment of cancer and the use of biomarker data to support the regulatory approval of ADVEXIN and improve the care of patients. The actual results may differ from those described in this release due to risks and uncertainties that exist in Introgen's operations and business environment, including Introgen's stage of product development and the limited experience in the development of gene-based drugs in general, dependence upon proprietary technology and the current competitive environment, history of operating losses and accumulated deficits, reliance on collaborative relationships, and uncertainties related to clinical trials, the safety and efficacy of Introgen's product candidates, the ability to obtain the appropriate regulatory approvals, Introgen's patent protection and market acceptance, as well as other risks detailed from time to time in Introgen's filings with the Securities and Exchange Commission including its filings on Form 10-K and Form 10-Q. Introgen undertakes no obligation to publicly release the results of any revisions to any forward-looking statements that reflect events or circumstances arising after the date hereof.
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Introgen Therapeutics, Inc.
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