Introgen's ADVEXIN(R) MAA Accepted for Review by European Medicines Agency
- Category: DNA RNA and Cells
- Published on Tuesday, 19 August 2008 02:00
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Novel Gene Therapy Has Potential to Offer New Personalized Approach to Treating Head and Neck Cancer
AUSTIN, Texas, USA | Aug. 18, 2008 | Introgen Therapeutics, Inc. (NASDAQ:INGN), a developer of targeted molecular therapies for cancer, and its subsidiary Gendux Molecular Limited, today announced that the European Medicines Agency (EMEA) has accepted for review the company's Marketing Authrorization Application (MAA) for ADVEXIN(R) (p53 tumor suppressor therapy) for the treatment of recurrent, refractory squamous cell carcinoma of the head and neck. ADVEXIN is an innovative gene therapy designed to restore p53 tumor suppression that is blocked in the majority of tumors. If approved, ADVEXIN will be the first gene therapy product approved for use in Europe. Introgen and Genedux announced the submission of the ADVEXIN MAA on June 30, 2008.
"This acceptance of the ADVEXIN MAA by the EMEA marks an historic point in the growth of personalized medicine and the treatment of head and neck cancer," said Max Talbott, Ph.D., Introgen's senior vice president of worldwide commercial development. "This action by the EMEA underscores the rapidly increasing importance of biomarkers in the development and regulatory approval processes for targeted therapeutics. We look forward to working with the EMEA during the ADVEXIN review process, which we hope will lead to the first gene therapy product in Europe."
The MAA is based upon a comprehensive clinical data package which includes the results from Introgen's open-label, multi-center, randomized, comparative Phase 3 study of ADVEXIN in patients with recurrent, refractory squamous cell carcinoma of the head and neck. This pivotal trial successfully achieved both the study's primary and secondary efficacy endpoints in the p53 biomarker patient population which were each prospectively designated. The primary efficacy endpoint of the Phase 3 study was survival in either the intent-to-treat (ITT) or biomarker patient population. The secondary efficacy endpoint was tumor response in either the ITT or biomarker patient population.
Previously announced results from this study include:
-- The percentage of patients surviving at six months demonstrated the clinical benefit of ADVEXIN in comparison to methotrexate. At the six month survival endpoint, 67% of ADVEXIN treated patients with tumor p53 profiles positive for ADVEXIN efficacy were alive compared to only 39% of the methotrexate patients with this tumor p53 profile. This difference was statistically significant (p = 0.0434).
-- A complementary statistical analysis (Cox Regression) evaluated the length of survival of patients in the biomarker population receiving ADVEXIN as compared to patients in the biomarker population receiving methotrexate. Results showed that patients with p53 tumor profiles positive for ADVEXIN efficacy demonstrated statistically significant increased survival benefit at both six months (p less than 0.0051) and overall (p = 0.0265) following treatment with ADVEXIN while patients with tumor p53 profiles negative for ADVEXIN efficacy
demonstrated an increased survival benefit with methotrexate treatment.
-- ADVEXIN significantly increased survival in patients with tumor p53 profiles positive for ADVEXIN efficacy compared to patients with tumor p53 profiles negative for ADVEXIN efficacy (7.2 months vs. 2.7 months; p less than 0.0001).
-- Patients treated with methotrexate whose tumor p53 profiles were positive for ADVEXIN efficacy had a median survival of only 4.3 months. Methotrexate improved survival in a different group of patients with tumor p53 profiles negative for ADVEXIN efficacy (median survival 5.9 vs. 2.7 months; p = 0.0112).
-- The majority of ADVEXIN responders (65 percent) had tumor p53 profiles positive for ADVEXIN efficacy compared to 50 percent of methotrexate treated patients with this profile. In patients with tumor p53 profiles negative for ADVEXIN efficacy the tumor response rate was 18 percent with ADVEXIN treatment
and 83% with methotrexate. The response differences between ADVEXIN and methotrexate were statistically significant (p =0.0108) indicating that these treatments are most effective in different groups of patients.
-- ADVEXIN demonstrated a superior safety profile to methotrexate.
"We believe that the ADVEXIN Phase 3 study data demonstrate clear and powerful evidence that the therpay results in significant survival and tumor response benefits for patients who possess p53 biomarkers that are positive for ADVEXIN efficacy," stated Robert E. Sobel, M.D., senior vice preseident, medical and scientific affairs at Introgen. "We are confident in the data package that was submitted to the EMEA, particularly in light of the increasingly important role that biomarker are playing in the area of drug development, and we eagerly await the result of the agency's review of the ADVEXIN MAA."
The MAA acceptance triggers the initiation of EMEA's regulatory review process. The review timelines are solely controlled by the agency and the company can make no guarentees as to the timing of the agency's response to the MAA.
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. ADVEXIN is considered an 'Orphan Drug' in the U.S. for the treatment of recurrent, refractory head and neck cancer, which, if approved, entitles the drug to extended market exclusivity for the approved indication. ADVEXIN is a registered trademark describing p53 therapy, developed by Introgen under exclusive worldwide licenses from The University of Texas M.D. Anderson Cancer Center.
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. In June 2008 Introgen submitted a BLA to the FDA requesting marketing approval for ADVEXIN p53 therapy to treat recurrent, refractory head and neck cancer. Simultaneously, Gendux Molecular Limited, an Introgen subsidiary, submitted a MAA to the EMEA for the same indication. ADVEXIN represents the first of a new class of tumor suppressor cancer therapy and is the first of its kind to be submitted for regulatory approval in the United States and Europe.
SOURCE: Introgen Therapeutics