Background/Purpose: Two randomized,
double-blind, placebo-controlled Phase III clinical trials showed that lesinurad
(200 or 400 mg) when added to allopurinol (200-900 mg) significantly increased
the proportion of gout patients achieving the serum uric acid (sUA) target of <6.0
mg/dL by Month 6, representing an approximate 2-fold increase with lesinurad 200
mg compared with allopurinol alone. Lesinurad was generally well tolerated,
particularly at the 200 mg dose, where the safety profile was comparable to allopurinol
alone, with the exception of a higher incidence in predominately reversible serum
creatinine (sCr) elevations. As renal
impairment and gout frequently coexist, the objective of the current pooled analysis
was to explore efficacy and safety endpoints in gout patients based on baseline
renal function.

Methods: Patient data were combined from 2 Phase III clinical
studies examining the efficacy and safety of lesinurad, a selective uric acid
reabsorption inhibitor (SURI), in combination with standard of care allopurinol
(200-900 mg) (CLEAR 1 [NCT01510158], CLEAR 2 [NCT01493531]). In current
analyses, patients were analyzed by baseline renal function using estimated creatinine
clearance (eCrCl; Cockcroft-Gault formula using ideal body weight): <60, <90,
and ≥90 mL/min.

Results: In total, 1208 patients were included in the analyses. Demographic characteristics, including age, gender, race,
weight, and BMI, were broadly similar between patient groups stratified by baseline renal function. Efficacy,
assessed by the proportions of patients with sUA <6.0 mg/dL at 6 and 12
months, was consistently greater (P<0.05)
for both lesinurad doses (200 mg and 400 mg) than placebo in all groups assessed
by baseline renal function (Table). There were no
consistent differences in TEAE rates in patients based on baseline renal
function (Table). sCr elevations occurred at higher rates in the lesinurad
groups (particularly the 400 mg dose) versus placebo, without evident
differences when analyzed by baseline renal function.

Conclusion: These combined analyses
from 2 Phase III studies indicate that lesinurad in combination with
allopurinol provides consistent, significant efficacy across all renal function
groups. Safety findings were consistent between treatment groups across all
renal function categories.

Table:
Efficacy and safety endpoints in CLEAR 1 and CLEAR 2 combined: stratification
by baseline eCrCl <60, <90, and ≥90 mL/min

*sCr resolution: sCr value returned to ≤1.2x baseline.
LESU, lesinurad; PBO, placebo; LOCF, last observation carried forward.