Vion Pharmaceuticals: FDA Allows Leukemia Trial to Resume

The clinical hold on a Phase III trial of Vion Pharmaceuticals’ Cloretazine in acute myelogenous leukemia has been lifted by the FDA after the company agreed to trial modifications. Vion now hopes that the new trial design will not reduce the efficacy of its lead anticancer pipeline drug.

The FDA has decided to lift the clinical hold on a pivotal study of Vion Pharmaceuticals’ cytotoxic drug, Cloretazine (laromustine; VNP40101M) following an agreed modification to the trial protocol. In this randomized Phase III trial, the combination of Cloretazine and cytarabine is being compared with placebo and cytarabine for the treatment of relapsed acute myelogenous leukemia (AML). The primary endpoint of the trial is objective response rate. A total of 420 patients will be enrolled in the trial.

The study was initiated in March 2005, but was suspended in May 2007 following a review of clinical data from the first 210 patients treated. This review showed that while response rates were higher in the Cloretazine and cytarabine arm, mortality was also higher.

In order to allow the study to continue, Vion has reached an agreement with the FDA over a modified trial protocol. Changes to the trial design include lowering the dose of Cloretazine, as well as the addition of prophylactic antibiotics, antifungals and growth factors for all patients in order to reduce toxicity. Before the trial can recommence, Vion must now submit a Special Protocol Assessment (SPA) to the FDA incorporating these modifications.

Cloretazine is also currently in a pivotal Phase II study as a single agent for newly diagnosed, poor risk AML. Vion intends to submit a New Drug Application (NDA) to the FDA in 2008 for this indication.

Results from clinical trials reported to date suggest that Cloretazine has promising activity in AML. Given the relatively high degree of unmet need in this therapy area, particularly in relapsed patients, the commercial prospects for this drug are relatively bright. However, an increasingly crowded late-phase AML pipeline means that the drug could face stiff competition if it reaches the market. Cloretazine’s potential competitors include Genzyme’s Clolar (clofarabine) which is also in a Phase III trial for the second-line treatment of AML. Undoubtedly, Vion will therefore hope that the reduced dose in the revised trial design does not compromise Cloretazine’s efficacy.