Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan). Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.5mg; study 2: 2.5-15mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed. Results: Most patients in study 1 (n=171) were white (74.9%); all patients were Japanese in study 2 (n=204). Least squares means (SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 +/- 2.9 for placebo, and -17.5 +/- 2.8, -29.1 +/- 2.8, -34.4 +/- 2.9 for verinurad 5, 10, 12.5mg, respectively. In study 2, results were -2.4 +/- 2.5 and -31.7 +/- 2.5, -51.7 +/- 2.6,-55.8 +/- 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo. Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study.