The drug is currently in late stage clinical trials and is intended primarily for the treatment of acute myelogenous leukaemia (AML). Cloretazine entered Phase III trials in combination with cytosine arabinoside (Ara-C) in relapsed AML in 2005, and Phase II trials in elderly patients with de novo poor-risk AML earlier this year.
There are also several other ongoing trials at various stages of development, with Cloretazine breing evaluated in other hematologic malignancies and solid tumours.
Cloretazine itself is an alkylating (DNA damaging) agent that showed a broad spectrum of anticancer activity in preclinical studies. It was curative in certain models, including cell lines that have been shown to be resistant to other alkylating agents such as BCNU (bischloroethylnitrosourea), cyclophosphamide and melphalan.
Vion suggest that Cloretazine could be used in combination with Ara-C to produce better anti-cancer activity, and the drug or its metabolite have also been shown to be capable of crossing the blood brain barrier in preclinical models - a frequent obstacle when trying to establish active concentrations of most drugs within the brain.
In January 2006 Vion received orphan drug status for Cloretazine for the treatment of AML in Europe, having already been granted the designation in the US. AML is estimated to affect approximately 32,000 people in the EU, and orphan drug status will entitle Cloretazine to ten years' market exclusivity in the indication of AML.
However, demonstration of quality, safety and efficacy is still necessary before the drug can be granted a marketing authorisation.
Ben Venue Laboratories is a Boehringer-Ingelheim company, and among the largest manufacturers of sterile injectable drug products in the US. It has a long-standing contract manufacturing relationship with the National Cancer Institute in the US, having held an uninterrupted series of contracts with the institute since the late 1960s.