GenasenseTreatment for Chronic Lymphocytic Leukemia
FDA Advisory Committee Reviews Genasense For Use in Advanced MelanomaBERKELEY HEIGHTS, NJ and BRIDGEWATER, NJ, May 3, 2004 –- Genta Incorporated (NASDAQ: GNTA) and Aventis (NYSE: AVE) presented results of their Phase 3 trial of Genasense (oblimersen sodium) Injection in combination with dacarbazine (DTIC) versus dacarbazine alone at the Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA). In the absence of increased survival, the committee voted that the evidence presented today did not provide substantial evidence of effectiveness, as measured by response rate and progression-free survival, to outweigh the increased toxicity of administering Genasense for the treatment of patients with metastatic melanoma who have not received prior chemotherapy. While the advisory committee’s recommendation is not binding, the FDA will consider it as the agency completes its Priority Review of the New Drug Application (NDA) for Genasense.
“We strongly believe in the potential of Genasense and what it represents to patients with advanced melanoma,” said Dr. Raymond P. Warrell Jr., Genta’s Chairman and Chief Executive Officer. “We are committed to its ongoing development and we will work closely with the FDA to determine the appropriate next steps.”
“Advanced melanoma represents a significant unmet medical need. While disappointing, the committee’s vote underscores the complexities of treating this devastating disease,” said Frank Douglas, MD, PhD, Executive Vice President of Drug Innovation and Approval and a Member of the Board of Management at Aventis. “We will work with our partners at Genta to address any outstanding questions from the FDA.”
Genta filed its NDA for Genasense in December 2003 and was granted Priority Review. An FDA response on the Genasense NDA is expected by June 8, 2004. The NDA for Genasense is based on results from a Phase 3 randomized trial of Genasense plus dacarbazine in patients with advanced melanoma. The study – the largest randomized trial ever conducted for advanced melanoma – enrolled patients at 139 sites in nine countries. Investigators randomly assigned 771 patients who had not previously received chemotherapy to either Genasense plus dacarbazine or dacarbazine alone. Patients who received Genasense in addition to dacarbazine showed significant improvement across clinical measures; a 51 percent improvement in median progression-free survival (74 days vs. 49 days); an improvement in durable response rate of = 6 months, (13 patients vs. 5 patients); and a 72 percent increase in overall anti-tumor response rate (11.7 percent vs. 6.8 percent).
During the meeting, the company also presented additional information on complete responders that were not part of the original NDA submission, and that have not been confirmed by the FDA. Six additional patients were identified who achieved complete responses in the follow-up period in the Genasense plus dacarbazine group, yielding a total of 11 complete responses. In this update, no additional complete responders were identified in the dacarbazine alone group.
In a randomized clinical trial in which patients received Genasense combined with dacarbazine (n=371) compared to dacarbazine alone (n=360), the most frequent serious adverse event occurring in = 5% of patients was fever (5.9% vs. 3.1%, respectively); the most frequent Grade 3 or 4 adverse events occurring in = 5% of patients were neutropenia (21.3% vs. 12.5% respectively), thrombocytopenia (15.6% vs. 6.4%), leukopenia (7.5% vs. 3.9%), anemia (7.0% vs. 4.7%), and nausea (7.0% vs. 2.5%).
Genasense inhibits production of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced apoptosis (programmed cell death). By reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current treatments for advanced melanoma. Genta and Aventis are pursuing a clinical development program with Genasense evaluating its potential to treat various forms of cancer.
About Advanced Melanoma
Advanced melanoma is the most deadly form of skin cancer because it has spread throughout the body forming secondary tumors. The incidence of melanoma has increased more rapidly than any other cancer, and has more than doubled in the last 30 years. According to the American Cancer Society, more than 55,000 cases of melanoma will be diagnosed in the U.S. in 2004. Melanoma is the number one cause of cancer death in the United States for women aged 25 to 29, and it ranks second in incidence to breast cancer in women aged 30-34. Globally, 132,000 melanoma skin cancers will occur globally every year, according to the World Health Organization.
Genta Incorporated is a pharmaceutical company 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 RNA and DNA-based Medicines and Small Molecules. Genasense™ (oblimersen sodium) Injection, the Company's lead drug from its RNA-DNA Medicines program, is being developed with Aventis and is currently undergoing late-stage, Phase 3 clinical testing for additional indications. The leading drug in Genta’s Small Molecule program is GaniteÒ (gallium nitrate injection), which the Company is exclusively marketing in the U.S. for treatment of patients with cancerrelated hypercalcemia that is resistant to hydration.
Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. In 2003, Aventis generated sales of € 16.79 billion (US $18.99), invested € 2.86 billion (US $3.24) in research and development and employed approximately 69,000 people in its core business. Aventis corporate headquarters are in Strasbourg, France. The company's prescription drugs business is conducted in the U.S. by Aventis Pharmaceuticals Inc., which is headquartered in Bridgewater, New Jersey. For more information, please visit: www.aventis-us.com
Posted: May 2004
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- Genta Completes Appeal of FDA Decision for Genasense in CLL - October 25, 2007
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- Genta Announces the Company Will Appeal FDA Action on New Drug Application of Genasense in Chronic Lymphocytic Leukemia - February 6, 2007
- Genta Receives Non-Approvable Notice for Application of Genasense in Patients With Chronic Lymphocytic Leukemia - December 15, 2006
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- Genta Initiates New Drug Application for Genasense in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia - June 30, 2005
- Genta Announces Withdrawal of New Drug Application for Genasense in Melanoma - May 13, 2004
- Genta and Aventis Announce Genasense Expanded Access Program for Patients with Advanced Melanoma - April 20, 2004
- Aventis and Genta Announce FDA Acceptance and Priority Review of New Drug Application for Genasense in Advanced Melanoma - February 6, 2004