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FDA Says Confirmatory Data Needed to Approve Oblimersen Sodium in Chronic Lymphocytic Leukemia

BERKELEY HEIGHTS, N.J., March 17 /PRNewswire-FirstCall/ -- Genta Incorporated (NASDAQ:GNTA) announced that the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) has decided that available data are not adequate to support approval of Genasense(R) (oblimersen sodium) Injection for treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL). In a decision issued in response to an appeal filed by Genta in October 2007, CDER acknowledged that complete response, which was the primary endpoint in the pivotal trial, was an appropriate endpoint for assessing efficacy. FDA also agreed that this endpoint was achieved, and that those results supported the efficacy of the drug. However, CDER concluded that at present there was insufficient "confirmatory evidence" in the New Drug Application (NDA) to approve the drug.

CDER recommended two alternatives for exploring the efficacy of Genasense that could provide such confirmatory evidence. One option is to conduct an additional clinical trial. The other option is to collect additional information regarding the clinical course and progression of disease in patients from the previous pivotal trial in order to ascertain whether those data contain sufficient confirmatory evidence. The Company currently plans to pursue both of these options.

"In concluding this process, we are pleased that CDER recognized the merit of our completed study, but more importantly has clarified a path to regulatory approval in this important indication," commented Dr. Loretta M. Itri, Genta's President, Pharmaceutical Development, and Chief Medical Officer. "Our approach mirrors our strategy for Genasense in melanoma in which a smaller Phase 3 trial, expected to complete accrual later this year, seeks to confirm efficacy by focusing on patients who derived maximum benefit in a large randomized trial. In parallel with collection and analysis of existing data in CLL, Genta has developed a new clinical trial, and the Company will file its draft protocol seeking formal Scientific Advice at the May meeting of the European Medicines Agency (EMEA). Genta greatly appreciates the professional and collaborative communications with FDA during this process, and we look forward to working closely with FDA in addressing their recommended options for securing the confirmatory data."

Proposed Confirmatory Trial of Genasense in CLL
The proposed protocol, based on results obtained during the previous trial, is a randomized controlled trial at first or second relapse in patients who are "non-refractory". All patients will receive fludarabine plus cyclophosphamide (Flu/Cy) - an accepted standard of care - and they will be randomly assigned to receive Genasense or no additional therapy. The trial will seek to confirm that the addition of Genasense increases complete responses (CR) in patients who receive Flu/Cy chemotherapy.

In the preceding Phase 3 trial, 241 patients with relapsed or refractory CLL were randomly assigned to receive Flu/Cy with or without Genasense. This study achieved its primary endpoint - an increase in the proportion of patients who achieved CR (17% vs. 7%; P=0.025). By definition, CR represents the complete elimination of all clinical signs of leukemia, combined with the elimination of leukemia-related symptoms. The duration of CR was also significantly longer for patients treated with Genasense (i.e., median not yet reached but exceeding 36 months in the Genasense group compared with 22 months for the Flu/Cy-only group).

In patients predefined as "non-refractory" (N=101), who are the focus of the proposed trial, the CR rate was 25% (13 of 51) in the Genasense group compared with 6% (3 of 50) in the Flu/Cy-only group (P=0.016). Extended followup has also demonstrated superior survival for patients who achieved CR in the Genasense group.

A scientific report of the safety and efficacy findings from the preceding study was published in the Journal of Clinical Oncology (25:1114, 2007).

About Chronic Lymphocytic Leukemia
CLL is the most common form of leukemia in adults. According to the American Cancer Society, approximately 8,000 patients will be diagnosed this year. More than 60,000 people in the U.S. currently have CLL. The disease arises in lymphocytes, a type of white blood cell that normally produces antibodies and serves important immune functions. Patients with CLL typically develop symptoms that may progress over a period of years, ultimately producing a generalized depression of immunity, marked increases in the size of spleen, liver and lymph nodes, and impaired production of other normal blood cells. Eventually, these problems may cause life-threatening complications, such as overwhelming infections and fatal bleeding. More information about CLL can be accessed at the website for the Lymphoma Research Foundation.

Source: Genta Incorporated

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