Staff Writer

EpiCept Corp. said Phase III data on Ceplene, its lead product candidate in acute myeloid leukemia (AML) validated leukemia-free survival as a surrogate endpoint for overall survival in AML patients in complete remission.

EpiCept presented data for the 320-patient, pivotal trial at the annual European Hematology Association Congress (EHA) in Copenhagen, Denmark, in hopes of providing additional support for its marketing authorization request in Europe and with the aim of facilitating a pre-new drug application meeting with the FDA.

In March the European Committee for Medicinal Products for Human Use issued a negative opinion regarding marketing authorization for Ceplene. EpiCept has formally requested a re-examination of that opinion, which could occur in the third quarter of 2008.

EpiCept CEO and President Jack Talley told BioWorld Today that while the drug is still under review by the European Medicines Agency, "the most significant thing is that these data add to the statistical robustness argument in favor of approval." The company conducted the trial not because of an agency requested more information, but rather to provide additional validation of leukemia-free survival (LFS) as a primary endpoint.

And the trial accomplished that mission, he said.

In a poster presentation cancer statistician Marc Buyse showed that while the extension of overall survival (OS) duration is a principal goal of all cancer therapies, leukemia-free is likely to be a better endpoint for AML since overall survival may be confounded by alternative salvage therapies and unrelated events.

In addition, in a weighted linear regression analysis between estimates of LFS and OS at specific time points and between the estimated effects of Ceplene with IL-2 on LFS and OS, researchers found a high correlation between the country-specific Kaplan-Meier estimates of 24-month LFS and 36-month OS in both treated and untreated groups. Similar correlations also were found between 24-month LFS and 48-month and 60-month OS. In addition, country-specific hazard ratios demonstrated that the treatment effect of Ceplene with IL-2 on LFS and OS were found to be highly correlated.

Still, Talley acknowledged that "you can't make a survival claim without a survival outcome." However, he said he thinks the results "certainly lead most clinicians to believe that leukemia-free survival is an appropriate endpoint for them to focus on, and that improving leukemia-free survival will ultimately lead to an improvement in overall survival in their patients."

And he said that the European agency called EpiCept's approach to extended LFS "revolutionary."

"This is the first and the only product that has ever been shown to extend the disease-free period and prevent relapse in AML patients." Talley said. "There are other drugs that are under study, with the goal of improving response rates, meaning the induction of remission, but this is the only drug that has ever been shown to improve the duration of remission."

Talley said that timeline is a factor in developing a drug targeting leukemia-free survival. "Once you decide to do a Phase III trial in this indication, you are committing yourself to a three-year primary endpoint. And we don't believe anyone is close from a competitive standpoint," he added. He said an EMA decision is expected at the end of July, and said the company could meet with the FDA by the end of the year.

In a separate poster presentation at EHA, EpiCept released new findings from another pivotal Phase III study of Ceplene demonstrating that AML patients maintained their quality of life while undergoing treatment with Ceplene in combination with low-dose Interleukin 2.

Talley said that trial data, which had never before been publicly released, "showed that patients were able to tolerate twice-daily subcutaneous injections of Ceplene and Interleukin 2 with an equivalent quality of life to the untreated control group. In summary, he said "a very high level of patient tolerability was observed in the trial."

Shares of Epicept (NASDAQ:EPCT) gained 4 cents, or 10 percent, to close at 44 cents.