Genasense(TM) Reported Active in Combination with Chemotherapy in Multiple Myeloma
Results Show Chemosensitization with Thalomid(R), Velcade(TM) and Multi-drug Chemotherapy
BERKELEY HEIGHTS, N.J., Dec. 9 /PRNewswire-FirstCall/ -- Genta Incorporated (Nasdaq:GNTA) announced results from several studies that suggest Genasense(TM) (oblimersen sodium), the Company's lead anticancer compound, enhances the activity of many types of chemotherapy in patients with multiple myeloma. The results were presented by three investigative groups at the annual meeting of the American Society of Hematology (ASH) in San Diego, CA.
Bcl-2, the protein target of Genasense therapy, is expressed at high levels in patients with myeloma. The protein has been shown to block the onset of myeloma cell death that would otherwise be triggered by chemotherapy. By blocking production of Bcl-2, Genasense may overcome the inherent resistance of myeloma to anticancer treatment. Genta is broadly exploring the use of Genasense as a means of enhancing the activity of chemotherapy for myeloma in Phase 2 and Phase 3 trials.
In a Phase 1-2 clinical study from the University of Maryland, 25 patients with advanced myeloma were treated with escalating doses of Genasense and thalidomide (Thalomid(R); Celgene Corp.), plus high-dose dexamethasone. All patients had received extensive prior therapy. Twenty-three of 25 (92%) had previously progressed despite having undergone stem cell or allogeneic transplantation. All had previously received dexamethasone, and 11 had previously received thalidomide. To date, 20 patients have completed induction therapy and are evaluable for response. Twelve of the 20 patients (60%) have achieved a major clinical response, including 2 complete responses, 4 near-complete responses, and 6 partial responses. Four other patients had a minor response. With a median of 7.5 months, only 1 patient has relapsed, and 16 patients remain on study.
Updated results from a second clinical study were published in the November 16, 2003 issue of Blood by a group from Utrecht, The Netherlands. Ten patients with refractory myeloma participated in this trial, 8 of whom were refractory to a standard drug combination known as "VAD" (vincristine, doxorubicin, and dexamethasone). Patients were treated with Genasense plus VAD. Of the 9 patients who are currently evaluable, 4 have achieved a partial response, and 3 have achieved a minor response. Median progression-free survival was 6 months, and median overall survival has not yet been reached.
Finally, in a preclinical study conducted by investigators at Memorial Sloan-Kettering Cancer Center and Roswell Park Cancer Institute, Genasense was combined with bortezomib (Velcade(R) Millennium Pharmaceuticals, Inc.) in models of myeloma and non-Hodgkin's lymphoma. Using 6 different cell lines, Genasense was shown to amplify the apoptotic activity of Velcade. A separate experiment using NHL xenografts showed that the chemosensitizing enhancing activity of Genasense was schedule-dependent, and that maximal activity was observed when Genasense was given before dosing with Velcade rather than after.
"The development of new drugs capable of targeting unique pathways in lymphoma has created new opportunities to sensitize these cancers to traditional chemotherapy drugs," stated Dr. Owen O'Connor, Head of Laboratory of Experimental Therapeutics for Lymphoma, Memorial Sloan-Kettering Cancer Center. "Our data suggest that these two drugs, when administered in a particular order, can exquisitively sensitize lymphoma cells to cyclophosphamide, producing cures in animals receiving the triple combination. These approaches will no doubt pave the way for new trials that will explore the merits of using these drugs in a complimentary way with traditional chemotherapy programs."
"Multiple myeloma is the focus of considerable attention at Genta. Enrollment into our Phase 3 multiple myeloma trial has completed and will provide further clinical evaluation of the Genasense/dexamethasone regimen that was presented today," observed Dr. Loretta M. Itri, Genta's President, Pharmaceutical Development. "The combination data with Thalomid and Velcade are logical and promising extensions of our Genasense development program."
About Multiple Myeloma
Multiple myeloma is a cancer that arises in blood cells (called plasma cells) that normally reside in the bone marrow. Plasma cells normally produce antibodies that fight off infections. When cancer develops in plasma cells, these cells markedly increase in number, which can cause severe bone pain and fractures; however, their ability to produce antibodies is actually greatly reduced. Therefore, people with these conditions are highly susceptible to infections. Malignant plasma cells are known to contain a high amount of Bcl- 2 protein, which is targeted by Genasense. Further information about these diseases can be found at the website of the Multiple Myeloma Research Foundation: 206.204.218.38.
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.
This press release and the conference call to follow contain 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: SVY
Web site: genta.com
prnewswire.com
12/09/2003 08:01 EST |
