Research Summary

Does Epaminurad Safely and Effectively Lower Serum Urate in Gout?

Edited by:
Ashton L. Stahl

Key Highlights

  • Epaminurad markedly increased the proportion of patients achieving serum urate (sUA) <0.36 mmol/L by week 4 versus placebo.

  • sUA lowering was dose-dependent and sustained through weeks 8 and 12.

  • Safety and laboratory parameters were comparable to placebo over 12 weeks; most adverse events were mild.

  • Febuxostat 80 mg produced week 4 response rates similar to epaminurad 9 mg.

Epaminurad, a selective inhibitor of human urate transporter 1 (hURAT1), produced rapid, clinically meaningful reductions in serum urate (sUA) in adults with gout. By week 4, 54.05% (3 mg), 71.79% (6 mg), and 88.89% (9 mg) achieved sUA <0.36 mmol/L compared with 0% on placebo; the effect persisted through week 12. Safety signals were similar to placebo, and most events were mild. A febuxostat 80-mg reference arm showed broadly comparable week 4 response to epaminurad 9 mg (84.21% vs 88.9%), though no inferential testing versus febuxostat was prespecified.

Gout is the most common inflammatory arthritis, driven by sustained hyperuricemia and frequently complicated by comorbid cardiometabolic disease. Existing urate-lowering therapies (ULT) have limitations, including hypersensitivity with allopurinol, potential cardiovascular concerns with febuxostat, and drug interactions or hepatotoxicity with older uricosurics. A more selective uricosuric approach targeting hURAT1 may improve efficacy and safety.

In this multicenter, randomized, double-blind, placebo-controlled, dose-finding phase 2b trial conducted at 18 Korean centers, adults aged 19–70 years with gout and sUA ≥0.42 mmol/L received epaminurad 3, 6, or 9 mg once daily, febuxostat 80 mg (reference), or placebo for 12 weeks. All participants received gout-flare prophylaxis and therapeutic lifestyle guidance. The primary endpoint was the proportion achieving sUA <0.36 mmol/L at week 4; key secondary endpoints included sUA <0.30 mmol/L and change in sUA at weeks 4, 8, and 12. Safety assessments included adverse events (AEs) and laboratory measures.

Among 169 treated participants (99.40% male; mean age 48.26 years; baseline sUA 0.53±0.09 mmol/L), adherence exceeded 90% across groups. Week 4 sUA <0.36 mmol/L was significantly higher with epaminurad versus placebo across all doses (9 mg, 88.89%; 6 mg, 71.79%; 3 mg, 54.05%; all P <.0001), with consistent benefits at weeks 8 and 12.

Achieving sUA <0.30 mmol/L also favored epaminurad at week 4 (9 mg, 77.78%; 6 mg, 46.15%; 3 mg, 29.73%; all P ≤.0003 vs placebo) and remained higher at later visits. Mean percent sUA change at week 4 was −48.86% (9 mg), −42.58% (6 mg), and −25.24% (3 mg) versus +3.04% with placebo (all P <.0001 vs placebo); reductions persisted through week 12. Gout-flare incidence showed expected early-ULT variability (eg, week 4: 5.56% [9 mg], 12.82% [6 mg], 21.62% [3 mg], 2.70% [placebo]). Patterns were generally similar across active arms over time. No significant between-group differences emerged for mean liver enzymes or serum creatinine; isolated creatinine elevations (≥1.5× baseline) occurred infrequently and resolved mainly during treatment. Most AEs were mild; no serious drug-related events occurred.

Limitations include the 12-week duration, absence of prespecified statistical comparisons versus the active reference (febuxostat), and a study population that was almost entirely male, limiting generalizability. Larger, longer, head-to-head trials are needed to confirm comparative effectiveness and long-term safety.

“Epaminurad was effective at reducing sUA levels in patients with gout,” the researchers concluded. “The study also confirmed the safety and tolerability profile during 12 weeks of treatment.”

Reference
Jun JB, Lee HS, Kim SH, et al. Efficacy and safety of epaminurad, a potent hURAT1 inhibitor, in patients with gout: a randomized, placebo-controlled, dose-finding study. Arthritis Res Ther. 2025;27(1):113. doi:10.1186/s13075-025-03577-w.