Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced 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.