AR882 Lowers Serum Urate in Patients with Gout

Robert Keenan, MD, MPH

Credit: LinkedIn

AR882, the novel and selective urate transporter 1 (URAT1) inhibitor, demonstrated safe and efficacious serum urate (sUA) lowering, total crystal volume dissolution, and tophus resolution in patients with gout with a variety of demographics and baseline characteristics, according to the study “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,” presented at the American College of Rheumatology’s 2023 Convergence in San Diego, California.¹ The drug may also improve safety and efficacy compared to current therapies in this treatment population, including those with both subclinical crystal and clinically visible deposition.

The proof-of-concept, 3-month, phase 2b trial included 42 patients with gout and subcutaneous tophi. Investigators evaluated AR882 compared with allopurinol on the reduction of clinically visible tophi in this patient population using caliper measurements and Dual Energy Computer Tomography (DECT).

Patients were randomized to receive AR882 75 mg, once-daily AR882 50 mg plus allopurinol, or once-daily allopurinol up to 300 mg. Tophi measurements were obtained every 4 weeks for 6 months using calipers and patients were imaged with DECT at baseline and 6 months. The primary endpoint was changes in sUA at the 3-month mark and the secondary endpoints were the resolution of target tophus area and the change from baseline in target tophus crystal volume at the 6-month mark. Safety assessments, such as vital signs and electrocardiograms, were obtained throughout the trial.

In the intent-to-treat cohort, the mean baseline sUA level ranged between 9.1-9.6 mg/dL across treatment groups. At the 3-month mark, the mean sUA levels were reduced to 4.5 (±1.2), 4.7 (±1.4), and 6.1 (±2.0) mg/dL for 75 mg plus allopurinol, 50 mg plus allopurinol, and allopurinol, respectively. In the 75 mg AR882 cohort, 86% and 64% of patients achieved sUA levels of <6 and <5 mg/dL, respectively; in the 50 mg AR882 plus allopurinol group, 77% and 69% of patients achieved sUA levels of <6 and <5mg/dL, respectively. Results were compared with patients in the allopurinol group, where 46% and 23% of patients achieved sUA levels of <6 and < 5mg/dL, respectively.

At month 6, 29% (n = 4) patients in the AR882 75 mg demonstrated complete resolution of ≥1 tophus, compared with 8% (n = 1) in the AR882 50 mg plus allopurinol cohort and 8% (n = 1) in the allopurinol cohort. Patients treated with AR882 75 mg had a greater reduction of total urate crystal volume (-30.7%, -8.3 cm3) or allopurinol (-16.8%, -1.2 cm3) vs combination (-31.5%, -0.9 cm3) from baseline to 6 months on DECT. Data showed a 68% decrease in total urate crystal volume of the feet and ankles in the AR882 75 mg cohort after receiving once daily treatment for 6 months.

No serious adverse events were reported due to AR882 treatment, including abnormalities in the kidney or liver. The most frequent adverse event was gout flare, and mild or moderate adverse events included headache, diarrhea, and upper respiratory infection. However, gout flare was less frequent in patients treated with AR882 when compared with allopurinol.

References

1. ^{Keenan R, Cheng-Chung WEI J, Morris S, Mundell, P, 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. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.}