Consistent with interim findings reported in May 2008, this study of BCX-4208, a potent, rationally designed, orally available purine nucleoside phosphorylase (PNP) inhibitor, met its primary objectives of safety and tolerability.
In addition, BCX-4208 displayed dose-dependent reductions in peripheral blood lymphocyte counts, including subsets measuring B cells (CD20), total T cells (CD3), T helper cells (CD4) and T suppressor/cytotoxic cells (CD8).
Further, plasma levels of BCX-4208 increased with dose, and plasma uric acid levels showed dose-related reductions with BCX-4208. In addition, consistent with interim results, no evidence of clinical efficacy, a secondary objective, was observed in psoriasis patients with the doses and duration of administration tested.
The Phase IIa study was a randomized, double-blind, placebo-controlled, dose-ranging trial, which enrolled 66 patients with moderate to severe plaque psoriasis. BCX-4208 was administered once a day for six weeks at a dose of either 20mg or 120mg. Patients were monitored for at least four weeks following treatment. The primary objectives of the study were safety and tolerability. Secondary objectives included pharmacodynamic and pharmacokinetic measures, and clinical response.
In the Phase IIa trial, BCX-4208 was generally safe and well-tolerated at doses up to 120mg daily. Earlier this year, following review of a planned interim analysis of the Phase IIa trial, Roche terminated its license agreement for the development of BCX-4208 for autoimmune diseases and transplant. As a result, BioCryst regained worldwide rights to BCX-4208. Roche and BioCryst agreed to complete the Phase IIa trial.
William Sheridan, chief medical officer of BioCryst, said: “The pharmacokinetic and pharmacodynamic results extend our knowledge base of PNP inhibition in the clinic, confirm the specificity of the effect and suggest that BCX-4208 may have utility in diseases dependent on T cells, B cells, or uric acid.”