BioCryst Pharmaceuticals, Inc. announces favorable 52-week safety results and sustained efficacy from the extension phase of its randomized Phase 2b trial of ulodesine (BCX4208) added to allopurinol in patients with gout who had failed to reach the serum uric acid (sUA) therapeutic goal of <6 mg/dL on allopurinol alone, as well as positive Phase 2 safety results in patients with mild to moderate renal impairment.
In the original 12-week study, 279 patients were randomized. The extension to 52 weeks, in which 119 patients entered the final extension phase, concludes the Phase 2b trial and Phase 2 development program for ulodesine. Patients continued their blinded, randomized therapy of ulodesine at doses of 5 mg, 10 mg and 20 mg and placebo once-daily. Allopurinol 300 mg once-daily was administered in all study arms.
The results of the 52-week, blinded Phase 2b safety extension trial confirm that ulodesine continues to be generally safe and well-tolerated in gout patients who inadequately responded to allopurinol alone, many of which had multiple co-morbidities. No clinical adverse event signals were observed that distinguished ulodesine from placebo, either by type or by rate at the doses tested. No opportunistic or unusual infections were observed and no signal for other organ toxicities was detected. No fatal or life-threatening adverse events were observed in any of the treatment groups. It was previously reported that eligible patients responded favorably to a vaccine challenge at 16 or 20 weeks of ulodesine treatment, confirming maintenance of a healthy immune response. The previously observed lymphocyte plateau reached by 12 weeks of treatment remained unchanged in the 5 mg, 10 mg and 20 mg ulodesine arms through 52 weeks. No patients from the placebo or 5 mg discontinued study drug for confirmed reductions of lymphocyte or CD4+ cell counts below certain protocol-specified thresholds; through 52 weeks, one patient was discontinued from the 10 mg group, four patients from the 20 mg group and twelve patients from the 40 mg group for reductions in CD4+ cell counts. The 40 mg arm was discontinued after the 24-week analysis.
The approximate doubling of sUA response rates with ulodesine seen at 12 weeks was sustained through 52 weeks of treatment. After 52 weeks of treatment, ulodesine doses of 5 mg, 10 mg, and 20 mg/day showed response rates of 45%, 47% and 64% respectively, compared to 19% 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 the Phase 2b study. Gout flares over 52 weeks occurred in 7% of placebo-treated patients compared to 9-21% of patients treated with ulodesine.
“Over 115 patient-years of drug exposure solidifies our confidence in the long-term safety of ulodesine and its ability to provide sustained sUA control over time. These comprehensive results reduce the risk of ulodesine Phase 3 development. Ulodesine has demonstrated clinical safety and efficacy in a wide variety of gout patients, including those with mild to moderate renal impairment, as well as those with a risk of kidney stones,” said Dr. William P. Sheridan, Senior Vice President & Chief Medical Officer of BioCryst Pharmaceuticals. “We are sharing these long-term Phase 2 results with potential partners who are evaluating licensing ulodesine for Phase 3 development and commercialization. We remain focused on concluding our partnering discussions, while preparing materials and protocols for Phase 3 trials that would enable a partner to quickly initiate the pivotal program.”
In addition to the Phase 2b trial, BioCryst completed a small Phase 2 trial in patients with moderate renal impairment. In this 12-week trial, 20 patients were randomized to placebo (n=4), 5 mg (n=8) or 10 mg (n=8) in combination with 200 mg allopurinol per day. A total of 118 patients with mild to moderate renal impairment, based on the body surface area adjustment of the Cockroft-Gault formula, have been evaluated on study drug across the Phase 2 program. These trials confirmed that ulodesine can be used safely in patients with mild to moderate renal impairment, a common co-morbidity in gout patients.