Genta Incorporated said the Food and Drug Administration's (FDA) Centre for Drug Evaluation and Research (CDER) has decided that available data are not adequate to support approval of Genasense (oblimersen sodium) Injection for treatment of patients with relapsed or refractory chronic lymphocytic leukaemia (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," said Dr. Loretta M. Itri, president, pharmaceutical development, and chief medical officer, Genta. "Our approach mirrors our strategy for Genasense in melanoma in which a smaller phase III 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."
A scientific report of the safety and efficacy findings from the preceding study was published in the Journal of Clinical Oncology (25:1114, 2007).
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 US 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.
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 anticancer treatment. Genta is pursuing a broad clinical development program with Genasense evaluating its potential to treat various forms of cancer.