On Jul 14, 2009 Genta Incorporated announced publication of a paper that independently confirms the link of a key biomarker to overall survival in patients with advanced melanoma. The biomarker, a tumor-derived enzyme known as lactate dehydrogenase (LDH), is measured by a widely available blood test. Genta's recently completed Phase 3 trial of Genasense(R) in advanced melanoma, known as AGENDA, specified low-normal LDH as an enrollment criterion. Results for progression-free survival (PFS), a co-primary endpoint of AGENDA, are anticipated in the Fourth Quarter of this year. If positive, the AGENDA results are expected to support global regulatory applications for Genasense(R) in this indication.
A previous randomized Phase 3 trial compared outcomes of patients with advanced melanoma who were treated using standard chemotherapy (dacarbazine) with and without Genasense(R) (oblimersen sodium) Injection, the Company's lead anticancer compound. This trial showed that overall survival (OS) was strongly associated with baseline levels of LDH. While high levels of LDH have long been associated with poor outcome in melanoma and other cancers, the Genasense study showed a significant interaction with treatment outcome in a prospectively stratified randomized trial. A scientific article that describes efficacy and safety results from that study can be accessed here:
http://www.jco.org/cgi/content/abstract/JCO.2006.06.0483v1.
The new publication describes the statistical model that first elucidated an association between increasingly elevated levels of LDH and inferior OS in the previous trial, along with the prospective application of that model to data derived from a recent trial conducted by the European Organization for Research and Treatment of Cancer (EORTC), the largest European oncology cooperative group. The EORTC randomized patients with advanced melanoma to drug combinations that did not employ Genasense and showed no between-treatment differences. The investigators then aggregated data from their study to test the hypothesis generated in the Genasense trial: namely, that OS in advanced melanoma is inversely associated with increasingly elevated levels of LDH.
The new analysis from the EORTC trial confirmed that association and showed results that were highly congruent with observations from the Genasense study. Moreover, the EORTC analysis also confirmed that this association extended into the normal range: specifically, patients with low-normal LDH had extended survival, an observation first established in the Genasense study. Thus, the EORTC analysis provides strong and independent confirmation of the association between survival and LDH levels. The new information appears in the July issue of the European Journal of Cancer. An abstract of the publication can be viewed here:
http://www.ejcancer.info/article/S0959-8049(09)00282-2/abstract.
About AGENDA: AGENDA is a Phase 3, randomized, double-blind, placebo-controlled trial that is intended to support global registration of Genasense for patients with advanced melanoma. The study is designed to confirm certain safety and efficacy results from Genta's prior randomized trial of Genasense combined with dacarbazine in patients who have not previously received chemotherapy and who are identified by a biomarker (low-normal levels of LDH). The co-primary endpoints of AGENDA are PFS and OS. The trial has completed accrual of 315 patients. PFS results - a co-primary endpoint in this trial -- are anticipated in the Fourth Quarter of 2009.
About Genta: Genta Incorporated is a biopharmaceutical company with a diversified product portfolio that is focused on delivering innovative products for the treatment of patients with cancer.