The results of this 24-week, blinded safety extension confirm that BCX4208 was generally safe and well-tolerated, and sustained serum uric acid (sUA) control over time. Patients generated healthy immune responses to a vaccine challenge at 16 or 20 weeks of BCX4208 treatment. Following the successful outcome of this 24-week analysis, BioCryst is preparing for end of Phase 2 regulatory discussions to take place in the coming months.
In the original 12-week study, 279 patients were randomized and 160 patients entered the extension phase. Patients continued their blinded, randomized therapy of BCX4208 at doses of 5 mg, 10 mg, 20 mg, 40 mg and placebo once-daily. Allopurinol 300 mg once-daily was administered in all study arms.
This longer-term safety profile of BCX4208 is consistent with the 12-week primary analysis results originally reported in October 2011. BCX4208 added to allopurinol was generally safe and well-tolerated at all doses studied, and responses to vaccines indicated healthy immune function. The types and rates of adverse events through 24 weeks, including infections, were similar between the groups treated with BCX4208 and placebo. No opportunistic or unusual infections were observed.
The previously observed lymphocyte plateau reached by 12 weeks of treatment remained unchanged in the 5 mg, 10 mg and 20 mg BCX4208 arms through 24 weeks. The 40 mg study arm met a protocol-defined cohort stopping rule based on the number of withdrawals for CD4+ cell counts, and this arm was discontinued after week 24. No patients from the placebo, 5 mg or 10 mg cohorts discontinued study drug for confirmed reductions of lymphocyte or CD4+ cell counts below certain protocol-specified thresholds; through 24 weeks, a total of four patients were discontinued from the 20 mg group and eleven patients from the 40 mg group for reductions in CD4+ cell counts.
A healthy immune response was seen in all study arms in a vaccine challenge sub-study conducted in 84 patients. The vaccines were administrated at either 16 or 20 weeks of treatment, and responses were assessed by measuring changes in antibody titers 4 weeks later. The response rates to tetanus toxoid (50%-100%) and polyvalent pneumococcal vaccine (64%-67%) in patients treated with BCX4208 were similar to placebo-treated patients who received tetanus toxoid (50%) and pneumococcal vaccine (64%). The response rates for placebo-treated patients are consistent with responses in normal individuals reported in literature.
The approximate doubling of sUA response rates with BCX4208 seen at 12 weeks was sustained through 24 weeks of treatment. After 24 weeks of treatment, BCX4208 doses of 5 mg, 10 mg, 20 mg and 40 mg/day showed response rates of 40%, 50%, 46% and 55% respectively, compared to 25% for placebo. These results are consistent with the previously reported positive findings at the 12-week primary efficacy time point.
There was a low incidence of gout flares in this study. Gout flares over 24 weeks occurred in 5% of placebo-treated patients compared to 7-16% of patients treated with BCX4208.
“We are very pleased to confirm the continued favorable safety profile and sustained efficacy for BCX4208 as an add-on therapy for gout. The sustained efficacy, healthy immune responses to vaccines, and clean safety profile from 900 patient-months of drug exposure in this study provides a robust basis for Phase 3 trials,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “Based on these results, we have selected the 5, 10 and 20 mg doses of BCX4208 for further evaluation.”