Preclinical Results Show Genasense(TM) Synergizes with Campath(R) in Chronic Lymphocytic Leukemia
CHICAGO, June 4 /PRNewswire-FirstCall/ -- Genta Incorporated (Nasdaq:GNTA) today announced the publication of preclinical data that showed Genasense(TM) (oblimersen sodium), the Company's lead anticancer compound, enhances the effectiveness of Campath(R) (alemtuzumab; ILEX) against both chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL) cells. The results were reported by a group from St. Bartholomew's Hospital and the Royal London School of Medicine, London, UK, and were published in the Proceedings of the Annual Meeting of the American Society of Clinical Oncology (ASCO).
Genasense inhibits production of Bcl-2, a protein that is highly expressed in malignant cells from patients with both NHL and CLL. Bcl-2 is widely believed to be a fundamental cause of resistance to anticancer therapy in both illnesses. Previous studies from this research group showed that Genasense amplified the activity of another monoclonal antibody, Rituxan(R) (rituximab; Genentech/Idec), in CLL and NHL cells. Moreover, the synergy with Rituxan was independently confirmed in a separate in vivo study of NHL.
In the current study, fresh leukemic cells taken from patients with CLL were evaluated for the amount of cell death induced by Genasense or Campath, a monoclonal antibody that was recently approved for the treatment of patients with CLL. The effectiveness of Campath and Genasense each used alone was first evaluated, followed by the use of both drugs together. Both drugs used alone were shown to trigger cell death; however, pretreatment of these cells with Genasense followed by Campath markedly increased the amount of cell death compared with Campath used alone. The data for the fresh human CLL cells are depicted in the table below. (Similar results were also noted in experiments using human NHL cell lines.) Lastly, the use of Genasense pretreatment enabled a 5-fold reduction in the equivalent effective dose of Campath.
Treatment Apoptotic Level
(mean % of cell death)
Campath alone 56%
Genasense alone 83%
Genasense plus Campath 92%
"Our new findings corroborate prior observations from our laboratory, which show that Genasense increases the apoptotic activity of a number of chemotherapeutic agents," noted Dr. Finbarr Cotter, senior author on the publication. "Clinical use of Campath can be associated with significant immunosuppression in patients with advanced CLL, so we are particularly encouraged by the marked activity seen when using reduced levels of that agent. These results suggest that Genasense might be useful in circumstances when reduced doses of highly toxic anticancer drugs may be important."
About Genasense
Genasense works by inhibiting the production of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced cell death. By reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current anticancer treatments. Genasense is currently in multiple late-stage randomized clinical trials including malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL) and non-small cell lung cancer.
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. The Company's research platform is anchored by two major programs that center on oligonucleotides (RNA/DNA-based medicines) and small molecules. Genasense(TM) (oblimersen sodium), the Company's lead compound from its oligonucleotide program, is being developed with Aventis and is currently undergoing late-stage, Phase 3 clinical testing. The leading drug in Genta's small molecule program is Ganite(TM) (gallium nitrate injection), which the Company intends to launch later this year for treatment of cancer-related hypercalcemia that is resistant to hydration. For more information about Genta, please visit our website at: www.genta.com.
This press release contains forward-looking statements with respect to business conducted by Genta Incorporated. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the Company's Annual Report/Form 10-K for 2002.
SOURCE Genta Incorporated
CO: Genta Incorporated
ST: New Jersey
SU: VEN TDS
Web site: genta.com
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06/04/2003 09:00 EDT |
