Genasense(TM) plus Rituxan(R) Reported Active in Non-Hodgkin's Lymphoma
Monday December 8, 8:09 am ET
Data Demonstrate Synergistic Effect between Genasense(TM) and Rituxan(R)
BERKELEY HEIGHTS, N.J., Dec. 8 /PRNewswire-FirstCall/ -- Genta Incorporated (Nasdaq: GNTA - News) announced that investigators presented results from several scientific studies suggesting that Genasense(TM) (oblimersen sodium), the Company's lead anticancer drug, could be used to synergistically enhance the activity of Rituxan® (rituximab; Genentech/IDEC Inc.) in non-Hodgkin's lymphoma (NHL). The results were presented at the annual meeting of the American Society of Hematology in San Diego, CA.
Genasense blocks the production of Bcl-2 -- a cancer protein that is believed to contribute to the inherent resistance of cancer cells to anticancer treatment. Preclinical studies have shown that Bcl-2 is responsible for multi-drug resistance in lymphoma cells. By blocking the production of Bcl-2, Genasense is being broadly tested as a drug that can enhance the activity of current cancer therapy.
Two clinical studies reported early activity of the Genasense/Rituxan combination. The first study was a collaborative effort between The University of Texas-M.D. Anderson Cancer Center in Houston, TX and the Fox Chase Cancer Center in Philadelphia, PA. In this study, Genasense was administered as a 7-day infusion in weeks 1, 3 and 5, and Rituxan was given weekly for a total of 6 doses. To date, 20 patients with relapsed or refractory NHL, who had failed a median of two prior chemotherapy regimens, have been treated. All but three patients had previously received Rituxan. Fifteen patients are currently evaluable, 5 of whom have achieved major responses (1 complete response, 4 partial responses).
The second trial evaluated Genasense alone and in combination with a drug combination known as R-CHOP (Rituxan, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with mantle cell lymphoma. Mantle cell lymphoma is an aggressive form of NHL that is highly resistant to chemotherapy and generally considered incurable with conventional treatment. The study was designed to evaluate the effects of escalating doses of Genasense used alone (without chemotherapy), up to a maximum of 6 cycles. Upon disease progression, newly diagnosed patients who had not previously received chemotherapy would receive Genasense plus R-CHOP, and patients who had previously failed chemotherapy would receive other treatment. A total of 47 patients were enrolled: 19 who had not previously received chemotherapy and 28 who had relapsed from or were refractory to prior treatment.
Across all treatment groups, 11 patients (30%) remained stable without progression during all 6 treatment cycles when Genasense was used without chemotherapy. To date, 12 newly diagnosed patients have completed therapy with Genasense/R-CHOP. Five patients have achieved a complete response (CR + CRu), and 5 patients have achieved a partial response for an overall response rate of 83%. The remaining 2 patients have stable disease. In the 21 evaluable relapsed/refractory patients who had progressed after receiving a median of 2 prior chemotherapy regimens, 2 patients achieved a complete response (CR + CRu) and 9 patients achieved stable disease. Genasense did not appear to increase the toxicity of R-CHOP in these patients.
A recent report suggested that Rituxan could overcome Bcl-2-mediated resistance in NHL. The final study was designed to test whether the activity of Rituxan in an experimental model of NHL was enhanced by Genasense. Rituxan alone increased median survival of animals with NHL to 61 days. The combination of Rituxan plus Genasense resulted in a marked increase in survival; the median was not reached at 90+ days. These data confirm earlier results presented last year at the annual meeting of the American Association of Cancer Research (AACR) that demonstrated increased survival in preclinical models when Genasense was administered in combination with Rituxan: genta.com.
"In aggregate, these data suggest that Genasense can be safely combined with Rituxan in several clinical settings," noted Dr. Loretta M. Itri, Genta's President, Pharmaceutical Development. "Bcl-2 is highly expressed in lymphoma cells, and NHL will be an important major focus of future clinical investigations with Genasense."
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 and non-randomized clinical trials, including malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and non-small cell lung cancer. The Company has initiated the filing of a New Drug Application to the Food and Drug Administration for treatment of patients with advanced malignant melanoma using Genasense plus dacarbazine.
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 and 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 is exclusively marketing in the U.S. for treatment of patients with cancer-related hypercalcemia that is resistant to hydration. For more information about Genta, please visit our website at: www.genta.com. |
