Pooled phase III data reported for Zurampic (lesinurad) in hyperuricemia associated with gout- Ironwood Pharmaceuticals

Ironwood Pharmaceuticals has presented efficacy and safety data from two Phase III extension studies of Zurampic (lesinurad) for the treatment of hyperuricemia associated with gout, as well as pooled analyses from the two extension studies and from the three pivotal Phase III Zurampic clinical trials, in four poster presentations. Patients treated with lesinurad plus allopurinol in the CLEAR 1 and CLEAR 2 trials who continued treatment in the CLEAR extension study maintained target sUA levels over the full two years. Additionally, an increased proportion of patients who received placebo in CLEAR 1 and CLEAR 2 reached target sUA levels after crossing into the CLEAR extension study and receiving treatment with lesinurad plus allopurinol. The data from this extension study identified no new safety signals in patients continuing lesinurad plus allopurinol treatment in the CLEAR extension study relative to the safety profile observed for those receiving lesinurad plus allopurinol in CLEAR 1 and CLEAR 2.

An analysis of pooled data from patients receiving lesinurad plus XOI in the CLEAR 1, CLEAR 2 or CRYSTAL trials who continued treatment in the CLEAR and CRYSTAL extension studies examined the impact of treatment of lesinurad plus XOI on tophi and flares. The pooled analysis found that patients treated with lesinurad plus an XOI for up to two years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of gout flares.

Renal-related and kidney stone safety data were pooled from patients enrolled in the CLEAR 1, CLEAR 2 and CRYSTAL trials taking either lesinurad 200 mg plus XOI or lesinurad 400 mg plus XOI as well as patients enrolled in the CLEAR and CRYSTAL extension studies. These pooled safety data were compared against patients taking XOI alone in the three pivotal Phase III trials, to evaluate the impact on renal safety of extended lesinurad plus XOI treatment. The study concluded that, except for a higher rate of serum creatinine elevations, the majority of which resolved during the study period, lesinurad at the approved dose of 200 mg once-daily combined with an XOI demonstrated a comparable rate of renal adverse events to XOI alone.

Finally study integrated safety data for lesinurad based on patients who completed the CLEAR 1, CLEAR 2 and CRYSTAL trials taking either lesinurad 200 mg plus XOI or lesinurad 400 mg plus XOI, as well as the CLEAR and CRYSTAL extension studies. The integrated study concluded that lesinurad at the FDA-approved dose of 200 mg once-daily combined with an XOI demonstrated a consistent, acceptable safety profile, with rates of treatment-emergent adverse events comparable to XOI alone and lower than with lesinurad 400 mg once-daily plus XOI. There were no new safety concerns identified in the extension studies. All data were presented at the American College of Rheumatology (ACR) Annual Meeting.