hURAT1 Inhibitor Epaminurad Safely Reduces Serum Uric Acid in People With Gout

Epaminurad was well-tolerated and was effective at reducing serum uric acid (sUA) levels in patients with gout in a new study.1

“Urate-lowering therapy (ULT) is recommended for patients with frequent flares, tophi, or joint damage. The main options are xanthine oxidase inhibitors (XOIs; allopurinol and febuxostat) and uricosuric drugs (e.g. probenecid, benzbromarone). However, although these treatments are effective to some extent, there are areas where improvements are still needed with current ULTs; for example, allopurinol can cause allergic reactions, febuxostat may be associated with cardiovascular risk, and probenecid can be associated with nephrolithiasis and drug-drug interactions.2 Consequently, new therapeutic options are needed,” lead investigator Jae-Bum Jun, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, and colleagues wrote.1

Epaminurad is a novel selective human urate transporter 1 (hURAT1) inhibitor that eas evaluated in a multicenter, randomized, double-blind, placebo-controlled, dose-finding phase 2b clinical trial, which consisted of a standard-treatment reference arm with febuxostat (n = 19), a placebo arm (n = 38), and epaminurad arms of 3 (n = 37), 6 (n = 39), and 9 mg (n = 36) once daily for 12 weeks. Overall, 7 in the placebo, 2 in the febuxostat, 3 in the 3 mg, 2 in the 6 mg, and 3 in the 9 mg discontinued the study due to withdrawal of consent (n = 7), use of prohibited medication (n = 5), or adverse events (n = 4).1

Participants were aged 19–70 years with gout and sUA levels of at least 0.42 mmol/L. They received gout prophylaxis and followed therapeutic lifestyle changes, before being randomized to treatment arms. The study primarily assessed the proportion of patients with sUA level less than 0.36 mmol/L after 4 weeks of treatment.

The study included 169 patients that were almost all male (99.40%) with a mean age of 48.26 years (standard deviation [SD], 13.15), and a baseline sUA level of 0.53 mmol/L (SD, 0.09). All treatment groups had at least a 90% mean adherence to treatment.1

Jun and colleagues found that the proportion of patients with sUA levels of under 0.36 mmol/L at week 4 was significantly higher in each epaminurad group (9 mg, 88.89%; 6 mg, 71.79%; 3 mg, 54.05%) compared with placebo (0.00%) (all P <.0001), while the febuxostat group had a response rate of 84.21%. Furthermore, the proportion of patients reaching sUA levels of under 0.30 mmol/L was also statistically significantly greater than placebo (P <.0001 for 9 and 6 mg, P = .0003 for 3 mg). Statistical comparison was not performed for febuxostat groups.1

At weeks 8 and 12, the proportion of patients with sUA < 0.36 mmol/L and sUA < 0.30 mmol/L remained significantly higher in all epaminurad groups versus placebo (P < .0001 for both targets at all doses, except 3 mg at sUA < 0.30 mmol/L: P = .0114 at week 8, P = .0251 at week 12). Mean percent and absolute changes in sUA were also significantly greater in all epaminurad groups compared to placebo at week 4, with consistent outcomes through weeks 8 and 12.1

Adverse event rates were similar across epaminurad and placebo groups, with most events classified as mild. Additionally, no significant differences were observed between epaminurad and placebo groups in mean serum creatinine or liver function parameters.

“Epaminurad at doses of 3, 6 and 9 mg, was effective at reducing sUA levels in patients with gout, in a dose-dependent manner. The study also confirmed the safety and tolerability profile during 12 weeks of treatment. The results suggest that epaminurad has potential as a treatment for patients with gout," Jun and colleagues concluded.1

REFERENCES

1. 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 27, 113 (2025). doi: 10.1186/s13075-025-03577-w

2. Jenkins C, Hwang JH, Kopp JB, Winkler CA, Cho SK. Review of urate-lowering therapeutics: from the past to the future. Front Pharmacol. 2022;13:925219.