BioCryst Pharmaceuticals, Inc. has announced that BCX-4208 has successfully completed a Phase I, placebo-controlled, single ascending dose, pharmacokinetic and safety trial involving 84 healthy volunteers. The study, which evaluated the pharmacokinetic profile for this oral formulation, measured BCX-4208 inhibition of the target enzyme purine nucleoside phosphorylase (PNP), and included detailed safety evaluations of renal and liver function, hematologic parameters, immunological markers, and cardiac function as measured through continuous ECG monitoring, including detailed QTc evaluations.
Results from this Phase I study indicate that single doses of BCX-4208 ranging from 0.5 mg/kg to 3 mg/kg were well-tolerated among the broad spectrum of safety parameters being monitored. Additionally, BCX-4208 achieved a dose-related inhibition of PNP, which effectively increases the serum level of deoxyguanosine that is necessary for selective suppression of T-cell activation.
Based on these positive results, BioCryst intends to initiate a randomized, double-blind, escalating multi-dose Phase I trial with BCX-4208 to further evaluate its safety profile and pharmacokinetics in approximately 60 healthy volunteers beginning in the second quarter of 2005. “The results from our first trial are very encouraging, and we are committed to the development of BCX-4208 for the treatment of psoriasis and other T-cell mediated conditions where an oral therapy offers clear advantages and might greatly improve patient quality of life,” stated Dr. Charles E. Bugg, Chairman and CEO of BioCryst.
BCX-4208 is BioCryst’s second generation, more potent transition-state analog inhibitor of PNP. The complex of BCX-4208 and PNP has a long half-life (approximately 8 days) with suitable oral bioavailability, which supports BCX-4208 as a good candidate for chronic dosing in autoimmune diseases such as psoriasis. The clinical development program for BCX-4208 is being conducted under an Investigational New Drug Application filed with the FDA for treatment of psoriasis. In addition to psoriasis, BioCryst intends to investigate the potential of BCX-4208 for the treatment of other clinical conditions that are believed to involve T-cell activation, including rheumatoid arthritis, Crohn’s disease and transplant rejection.