BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) announced positive top-line results from a planned interim analysis of its ongoing Phase 2a, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of orally administered BCX4208 in patients with gout.
“This successful first clinical test of BCX4208 in patients with gout confirms this PNP inhibitor's ability to reduce uric acid levels in the blood and supports its continued evaluation as a potential treatment for patients with gout”
The study's primary endpoint is the change in serum uric acid concentration after 21 days of treatment compared to baseline concentration prior to treatment. Part one of the study randomized 60 gout patients with serum uric acid concentrations greater than or equal to 8 mg/dL to placebo or to one of three different doses of BCX4208, a purine nucleoside phosphorylase (PNP) inhibitor, administered once-daily for 21 days. All three doses of BCX4208 demonstrated a statistically significant reduction in serum uric acid levels compared to placebo at day 22. BCX4208 doses of 40 mg, 80 mg and 120 mg per day showed median reductions in serum uric acid levels of 2.7, 3.3 and 3.4 mg/dL, respectively.
The median reductions of serum uric acid concentrations for these three doses ranged from 32.2 to 34.6 percent of baseline level. BCX4208 also demonstrated a statistically significant difference in the proportion of subjects with uric acid levels less than 6 mg/dL, compared to subjects treated with placebo, on day 22. Among patients with a baseline uric acid concentration below 10 mg/dL, up to 63 percent showed uric acid levels below 6 mg/dL on day 22.
BCX4208 was generally safe and well-tolerated at the doses evaluated in part one of this study. Reductions in peripheral blood lymphocytes were observed in patients treated with BCX4208. The protocol included stopping rules for CD4+ cell counts below certain thresholds; no subjects were discontinued for this reason and all 60 subjects completed the first part of this study. Overall, the frequency of adverse events in each of the BCX4208 treatment groups was comparable to that observed in the placebo group. All patients received prophylactic medicine for gout flares; the incidence of gout flares observed was low. Additional studies designed to evaluate longer-term exposure are needed to further define the safety and tolerability profile of BCX4208.
Part two of the study, designed to sequentially evaluate the safety and efficacy of up to three higher doses of BCX4208, is now under way. Following completion of the study, detailed results will be submitted for presentation at an upcoming scientific meeting.
"Novel therapeutics are urgently needed for the growing patient population with chronic or frequently recurrent gout. The results from this study of BCX4208 are encouraging, since they reveal rapid and substantial urate lowering by targeting PNP with an oral compound," stated Robert Terkeltaub, M.D., VA Rheumatology Section Chief, San Diego Professor of Medicine. "BCX4208, the only PNP inhibitor in development for gout, could prove particularly useful in combination therapy strategies tailored to safely and effectively reduce the symptoms associated with high serum urate in difficult to treat gout patients."
"This successful first clinical test of BCX4208 in patients with gout confirms this PNP inhibitor's ability to reduce uric acid levels in the blood and supports its continued evaluation as a potential treatment for patients with gout," said Dr. William P. Sheridan, Chief Medical Officer at BioCryst. "We have started part two of this study and we are finalizing plans for an additional Phase 2 trial of BCX4208 as a monotherapy and in combination with allopurinol, a commonly used urate-lowering treatment for gout. During 2010 we expect to complete these studies, which should define dosing suitable for further development of BCX4208 for gout."