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 at: lymphoma.
About Genasense
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.
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. Two major programs anchor the Company's
research platform: 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
to the AGENDA Trial, 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 G4544, an oral formulation of the active ingredient in Ganite,
that has recently entered clinical trials as a potential treatment for
diseases associated with accelerated bone loss. The Company is also
developing Tesetaxel(R), a novel, orally absorbed, semi- synthetic taxane
that is in the same class of drug as paclitaxel and docetaxel. Ganite and
Genasense are available on a "named-patient" basis in countries outside the
United States. For more information about Genta, please visit our website
at: genta.
Safe Harbor
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
litigation;
-- the Company's ability to retain compliance with the NASDAQ's listing
qualifications; and
-- 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 2007
and its most recent quarterly report on Form 10-Q.
Genta Incorporated
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