CuraGen Corporation achieved preliminary top-line results from its phase II randomised, placebo-controlled clinical trial evaluating a single-dose of velafermin for the prevention of oral mucositis (OM) in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to autologous bone marrow transplantation. Analysis of this dose-ranging study showed a reduction in oral mucositis incidence in one of the three velafermin dose arms compared to placebo, although the primary endpoint, as evaluated by a predefined dose trend analysis did not reach statistical significance. Preliminary analysis of the 30-day safety results indicates that velafermin appears to be safe and well-tolerated in this severely ill patient population.
A total of 212 patients were equally randomized to the four treatment arms and included in the intent-to-treat analysis. A single-dose of velafermin 0.03 mg/kg resulted in an incidence of grade 3 or 4 OM of 18% compared to a placebo incidence of 37% (p=0.031), which is a 50% relative reduction. This effect was not observed at the higher doses of velafermin, claims a company release.
The phase II clinical trial was a randomised, double-blind, placebo- controlled trial evaluating a single administration of either placebo or one of three doses of velafermin given to patients one day after bone marrow transplantation. The primary endpoint for the study was the development of clinically significant grade 3 or 4 OM scored by the World Health Organisation (WHO) oral mucositis scale. The primary analysis of the study examined a linear trend in dose across the 0.03 mg/kg, 0.1 mg/kg, and 0.2 mg/kg velafermin arms compared to placebo. An analysis of each individual dose group versus placebo was also conducted, as well as the evaluation of secondary endpoints including duration of grade 3 and 4 oral mucositis, use of narcotic pain medications, time to neutrophil engraftment, and the incidence and duration of diarrhoea.
“We are encouraged with the analyses which we believe show potentially meaningful single-dose activity of velafermin for the prevention of oral mucositis at a safe and well-tolerated dose. These results will be discussed with experts and advisors in the field as we look forward to confirming and expanding this observation in additional phase II studies,” stated Tim Shannon, executive vice president of research and development and chief medical officer at CuraGen.
"Completing this phase II trial ahead of our previously stated milestone is a significant accomplishment for CuraGen. We are encouraged by these preliminary results on velafermin as they were generated in a well-controlled, randomised phase II study," stated Patrick Zenner, interim chief executive officer and chairman of CuraGen.
"Significant progress has been made at CuraGen throughout 2005. Clinical results have been achieved on our oncology pipeline, including velafermin and PXD101, we have reduced our outstanding convertible debt, and we have focused our resources on our most advanced therapeutic opportunities. Furthermore, 454 life sciences began commercialising its breakthrough whole genome sequencing technology with its marketing and distribution partner, Roche Applied Sciences. In 2006, we look forward to continued progress with our therapeutic pipeline and 454's commercialisation," added Zenner.
Velafermin, also known as fibroblast growth factor-20 (FGF-20) or CG53135 is a novel protein therapeutic, discovered by CuraGen, that appears to promote both epithelial and mesenchymal cell proliferation.
CuraGen has completed a phase II clinical trial investigating a single- dose of velafermin for the prevention of OM in cancer patients undergoing bone marrow transplant. In this trial, a single-dose of velafermin was administered to patients before the onset of OM symptoms to evaluate velafermin's ability to decrease the incidence and duration of OM compared to placebo.