Novel selective URAT1 inhibitor shows promise in gout

AR882, a novel URAT1 inhibitor, resulted in serum uric acid (sUA) lowering, dissolution of crystals, and resolution of tophi after 6 months of treatment in participants with gout. The drug may offer better efficacy and safety than existing therapies for gout. It was well-tolerated and easy to use as a once-daily therapy that does not require titration.

A proof-of-concept phase 2 trial evaluated the effect of AR882 compared with allopurinol on the clinically visible tophi in participants with gout [1]. The trial recruited 42 participants with subcutaneous tophi, who were randomised to receive once-daily AR882 75 mg, once-daily AR882 50 mg + allopurinol, or once-daily allopurinol up to 300 mg. Tophi were measured every 4 weeks for 6 months with a calliper. Participants also underwent imaging with Dual Energy Computer Tomography (DECT) at baseline and after 6 months. The primary efficacy endpoint was sUA change after 3 months. Safety data were collected throughout the study.

The results were presented by Prof. Dr Robert Keenan (Duke University School of Medicine, NC, USA). The mean baseline sUA level was 9.4 mg/dL. After 3 months, these levels were reduced to 4.5 (±1.2), 4.7 (±1.4), and 6.1 (±2.0) mg/dL in the AR882 75 mg, AR882 50 mg + allopurinol, and allopurinol groups, respectively. After 6 months, at least 1 tophus had completely resolved in 4 participants (29%) in the AR882 75 mg group, compared with 1 participant (8%) in the AR882 50 mg + allopurinol group and 1 participant (8%) in the allopurinol group. The absolute change in crystal volume on DECT was -8.3, -0.9, and -1,2 cm³ in the 3 groups, respectively. Prof. Keenan said the complete resolution is “practically unheard of” after 6 months of therapy, especially with an oral agent. He added that AR882 treatment was not associated with any serious adverse events. The most frequent adverse event was gout flare, which had a lower rate in the AR882 treatment groups than in the allopurinol group. There were no cardiovascular, renal, or hepatic safety signals.

Prof. Keenan concluded that AR882 could potentially treat the entire spectrum of gout patients.

1. Keenan RT, et al. AR882, an efficacious and selective URAT1 inhibitor for patients with chronic gouty arthritis and subcutaneous tophi: results from a global, prospective, proof-of-concept trial using dual-energy computed tomography. L15, ACR Convergence 2023, 10–15 November, San Diego, USA.

Medical writing support was provided by Michiel Tent.
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Posted on 1 December, 20231 December, 2023