FDA Indicates That Genasense(R) Approval in Chronic Lymphocytic Leukemia Will Require Additional Confirmatory Data

[Guest guest]

Posted on Mon, Mar. 17, 2008

FDA Indicates That Genasense® Approval in Chronic Lymphocytic Leukemia Will

Require Additional Confirmatory Data

Genta Incorporated

BERKELEY HEIGHTS, N.J., March 17 -- 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® (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).

http://www.sunherald.com/447/v-print/story/434761.html