EpiCept's Ceplene NDA rejected

The US Food and Drug Administration (FDA) has refused to accept for filing EpiCept Corporation's New Drug Application (NDA) for Ceplene (histamine dihydrochloride), the company's experimental treatment for acute myeloid leukaemia (AML). The federal agency recommended that EpiCept conduct an additional pivotal trial before resubmitting the application.

Ceplene, which EpiCept is developing for AML remission maintenance and the prevention of relapse in patients in first remission, is intended to be co-administered with low-dose interleukin-2 (IL-2). According to the FDA, a preliminary review of the Ceplene NDA did not establish Ceplene's therapeutic contribution in the drug combination.

The agency recommended that EpiCept conduct a confirmatory pivotal trial assessing Ceplene's contribution, using overall survival as a primary endpoint, before resubmitting the NDA. EpiCept said it intends to request a meeting with the FDA as soon as possible to discuss whether it will be possible to resubmit the application without conducting another clinical trial. The company also noted that it has the right to file the marketing application even over the FDA's objections.

The NDA already contains a phase III study that demonstrates that the drug combination provided a statistically significant improvement in leukaemia-free survival without impacting patients' quality of life. It also contains the results of two meta-analyses designed to help isolate Ceplene's efficacy, which were included at the FDA's request.
The first meta-analysis confirmed the lack of clinical efficacy of IL-2 monotherapy for the indication, while the second demonstrated Ceplene's contribution, according to EpiCept.

EpiCept president and CEO Jack Talley said he was "surprised and obviously very disappointed" by the FDA's refusal to file the application. Ceplene is EpiCept's lead drug candidate, although the company also has a prescription topical analgesic cream in late-stage clinical development for long-term relief of pain associated with peripheral neuropathies, as well as two oncology drug candidates also in clinical trials.

EpiCept submitted the Ceplene NDA in late June and requested a priority review, meaning that the company had hoped to receive a decision from the FDA by December of this year.

Ceplene was approved in the European Union in 2008. Marketing applications for the drug are currently under review in Canada and Israel.