Submission Seeks Approval of Genasense in Relapsed/Refractory Patients
BERKELEY HEIGHTS, N.J., Oct. 25 /PRNewswire-FirstCall/ -- Genta Incorporated (Nasdaq: GNTA) announced that the Company has completed the filing of the Company's formal appeal to Dr. Janet Woodcock, Acting Director of the Center for Drug Evaluation Research (CDER), at the U.S. Food and Drug Administration (FDA). The appeal asks that CDER approve the use of Genasense(R) (oblimersen sodium) Injection plus chemotherapy for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In December 2006, FDA issued a non-approvable letter for the Company's New Drug Application (NDA) for Genasense in CLL. This appeal has been submitted in accordance with the Formal Dispute Resolution process that exists within CDER. Responses to CDER appeals are typically made within 30 to 60 days.
The appeal reflects several considerations, including but not limited to the following:
- Complete responses -- the primary endpoint of the trial - were more
than doubled in the Genasense group compared with controls who received
chemotherapy alone. The difference was statistically significant.
- Complete response confers clinical benefit in CLL. By definition, a
complete response requires elimination of all evidence of disease,
normalization of blood counts, and resolution of symptoms.
- The median duration of complete response in patients who received
Genasense has exceeded 3 years, at least 50% longer compared with
controls, which is clinically meaningful and statistically significant.
Survival information from this study will be updated at the annual
meeting of the American Society of Hematology (ASH) in December 2007.
- The Genasense study is the only randomized controlled trial ever
conducted in this population.
- The number, type, and severity of adverse reactions encountered with
Genasense were comparable to other leukemia drugs, which are readily
managed by specialists.
Genasense in CLL
In the pivotal Phase 3 trial, patients with relapsed or refractory CLL were randomly assigned to receive fludarabine plus cyclophosphamide (Flu/Cy) chemotherapy with or without Genasense. This trial - the first randomized study ever conducted in this population - achieved its primary endpoint, which was a statistically significant increase in the proportion of patients who achieved a complete or nodular partial response (CR/nPR) (17% vs. 7%; P=0.025). In addition, the duration of CR/nPR was significantly longer for patients treated with Genasense (median = not reached but exceeding 36 months in the Genasense group vs. 22 months for patients treated with chemotherapy alone).
Prior to randomization on this trial, patients were prospectively stratified according to criteria that reflected their responsiveness to prior chemotherapy. The CR/nPR response to Flu/Cy alone was both equally poor (6-7%) and numerically inferior in all stratification groups. Clear trends, evident across all strata, suggested that the best response to Genasense occurred in patients who had received less extensive therapy. In addition to achieving the prospectively defined, intent-to-treat primary endpoint, patients in the Genasense group who were protocol-defined as "non-refractory" to fludarabine (comprising more than 40% of the total population) achieved:
- A four-fold increase in CR/nPR (25% [13/51] vs. 6% [3/50]; P = 0.016)
- Increased time-to-progression (median = 12 months. vs. 10 months;
P = N.S.)
- Increased overall survival (median not reached but exceeding 39 months.
vs. 33 months; P = 0.05)
A scientific report of the safety and efficacy findings from this pivotal study was published earlier this year in the Journal of Clinical Oncology (25:1114, 2007).
Grade 3 or Grade 4 adverse events that occurred during treatment or within 30 days from last treatment in an increased percentage of patients in the Genasense group included, but were not limited to, thrombocytopenia, nausea, and intravenous-catheter complications. Adverse events resulted in discontinuation of therapy in an equal percentage of patients in both groups. Nine patients in the Genasense group and 5 patients in the chemotherapy-alone group had adverse events that resulted in death, including two patients in the Genasense group who died from complications associated with tumor lysis and infusion-related reactions.
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 at: http://www.lymphoma.org.
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.
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: DNA/RNA-based Medicines and Small Molecules. Genasense(R) (oblimersen sodium) Injection is the Company's lead compound from its DNA/RNA Medicines program. Genta is currently recruiting patients for a global Phase 3 trial of Genasense in patients with advanced melanoma. The leading drug in Genta's Small Molecule program is Ganite(R) (gallium nitrate injection), which the Company is exclusively marketing in the U.S. for treatment of symptomatic patients with cancer related hypercalcemia that is resistant to hydration. The Company has developed an oral formulation of the active ingredient in Ganite that is currently undergoing initial clinical trials as a potential treatment for diseases associated with accelerated bone loss. Genta is partnered with IDIS (http://www.idispharma.com) on a program whereby both Ganite(R) and Genasense(R) are available on a "named-patient" basis in countries outside the United States. For more information about Genta, please visit our website at: http://www.genta.com.
This press release may 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. Forward- looking statements include, without limitation, statements about:
- the Company's ability to obtain necessary regulatory approval for
Genasense(R) from the U.S. Food and Drug Administration ("FDA") or
European Medicines Agency ("EMEA");
- the safety and efficacy of the Company's products or product candidates;
- the Company's assessment of its clinical trials;
- the commencement and completion of clinical trials;
- the Company's ability to develop, manufacture, license and sell its
products or product candidates;
- the Company's ability to enter into and successfully execute license and
collaborative agreements, if any;
- the adequacy of the Company's capital resources and cash flow
projections, and the Company's ability to obtain sufficient financing to
maintain the Company's planned operations;
- the adequacy of the Company's patents and proprietary rights;
- the impact of litigation that has been brought against the Company and
its officers and directors and any proposed settlement of such
- the other risks described under Certain Risks and Uncertainties Related
to the Company's Business, as contained in the Company's Annual Report
on Form 10-K and Quarterly Report on Form 10-Q.
The Company does not undertake to update any forward-looking statements. 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 on Form 10-K for 2006 and its most recent quarterly report on Form 10-Q.
The Trout Group
|SOURCE Genta Incorporated|
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