BioCryst Pharmaceuticals announced interim data from the ongoing Forodesine HCl phase-2 programme in patients with chronic lymphocytic leukaemia (CLL) and data from a healthy subject pharmacokinetic and pharmacodynamic study. The CLL study will continue with an amendment to study a new dosing regimen of oral Forodesine, 200 mg twice-daily.

An interim analysis was conducted on data from an exploratory phase-2 single-arm, open-label programme in patients with CLL whose previous treatment had failed. While this analysis showed that no partial or complete responses were observed, five out of 13 patients administered 200 mg of Forodesine HCl once-daily had substantial reductions in malignant lymphocytes, and at the time of the analysis, seven patients were still on study. Forodesine HCl was generally safe and well-tolerated at the 200 mg once-daily dose.

In a parallel, healthy subject, pharmacokinetic and pharmacodynamic study, BioCryst compared the effect of seven days of 200 mg Forodesine HCl dosed once-daily with seven days of 200 mg Forodesine HCl dosed twice-daily. The study demonstrated substantially increased drug exposure and pharmacodynamic effect in subjects administered Forodesine HCl 200 mg twice-daily. Drug exposure, as measured by AUC, increased by 63 per cent (P<0.001) for twice-daily dosing compared to once-daily dosing. Serum uric acid levels were reduced at steady state compared to baseline by 50.0 percent for twice-daily dosing compared to 23.5 per cent for once-daily dosing (p<0.001), indicating increased PNP enzyme inhibition with twice-daily dosing.

"The interim data demonstrates that Forodesine HCl has potential activity in patients with CLL," stated Dr William Sheridan, BioCryst's chief medical officer. "Based on these results and the normal subject pharmacokinetic and pharmacodynamic study results, we have amended the ongoing phase-2 study, and will now administer Forodesine HCl twice-daily to examine the potential benefits of increased drug exposure. We expect to provide an update on this trial by the end of 2009."

"In our experience to date, Forodesine HCl was very well tolerated by patients in this phase-2 study. We are pleased with these results and look forward to further testing to determine the efficacy of Forodesine HCl when administered twice-daily in patients with CLL," stated Dr Asher Chanan-Khan, associate professor of Oncology at Roswell Park.

Forodesine HCl is a transition-state analog inhibitor of the target enzyme purine nucleoside phosphorylase (PNP).

BioCryst is an integrated biopharmaceutical company utilizing crystallography and structure-based drug design to develop a deep pipeline of novel therapeutics targeting major illnesses.