After 12 weeks of treatment, the median sUA levels of patients with gout were reduced from 8.6 mg/dL to 3.6 mg/dL in the AR882 75 mg cohort and 5.0 mg/dL in the AR882 50 mg group.
Most patients with gout treated with AR882 achieved serum urate (sUA) levels below 5 of 4 mg/dL, 2 key thresholds for efficient flare and tophi reductions, according to data presented at the European Congress of Rheumatology (EULAR) 2023.1 The drug was well tolerated during a 12-week treatment period and those with comorbidities did not require adjustments in disease management.
Findings add to the growing body of evidence that AR882 can robustly lower sUA levels in this patient population, including those with various degrees of renal insufficiency.
“Despite gout being the most common inflammatory arthritis, there remains an unmet need for more effective treatment,” wrote Roy Fleischmann, MD, Metroplex Clinical Research Center, Rheumatology, Dallas, and colleagues. “AR882 is a novel, potent, and selective uric acid transporter 1 (URAT1) inhibitor in development for the treatment of gout and tophaceous gout.”
The randomized, multicenter, double-blinded, placebo-controlled, global phase 2b trial aimed to evaluate the safety, tolerability, and efficacy of AR882 compared with placebo in patients with gout. Investigators recruited adult patients (aged 18 to 75 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min among 20 sites in the United States, Taiwan, and Australia. Eligible patients met the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Gout Classification Criteria.
After adhering to gout flare prophylaxis for 10 days, patients received once-daily AR882 50 mg, AR882 75 mg, or placebo, for 12 weeks. Blood samples were collected and evaluated every 2 weeks to assess sUA and pharmacokinetics. The efficacy endpoint was the proportion of patients able to achieve sUA levels below 6, 5, 4, and 3 mg/dL and safety endpoints included vital signs and electrocardiograms.
In total, 140 patients were enrolled in the study, of which most (93.6%) were male and White (58%), followed by Asian (28%), and Black (15%). The median baseline sUA level was 8.6 mg/dL, the mean age was 54.3 years, and the mean body weight was 96.5 kg. The most common comorbidities were hypertension (47%), hyperlipidemia (35%), renal insufficiency (34%), arthritis (23%), diabetes (19%), cardiovascular disease (15%), lung disease (11%), and liver disease (5%).
After 12 weeks of treatment, the median sUA levels were reduced from 8.6 mg/dL to 3.6 mg/dL in the AR882 75 mg cohort and 5.0 mg/dL in the AR882 50 mg group. No changes were reported in those receiving the placebo. In the 75 mg group, 89%, 82%, 63% and 29% of patients achieved < 6, <5, <4 and <3 mg/dL, respectively, at week 12. In the 50 mg cohort, 78%, 50%, 8% of patients achieved < 6, <5 and <4 mg/dL, respectively.
No serious adverse events were reported in patients receiving AR882, although mild or moderate adverse events included headache, diarrhea, and upper respiratory tract infection. Throughout the study period, a total of 65 gout flares were reported, which were comparable among treatment groups.
Investigators believe that AR882 has the potential to offer improved efficacy with an acceptable safety profile when compared with existing therapies for gout and may aid in the treatment of patients across the gout spectrum, including those with severe or refractory disease.
"Current standards of care have been ineffective in addressing the underlying cause of gout and associated patient morbidity," Robert T Keenan, MD, MPH, MBA, Arthrosi's Chief Medical Officer, said in a statement earlier this year.2 "AR882 has not only demonstrated high response rates achieving the minimum sUA target of below 6 mg/dL needed to control the disease, but also demonstrated sufficient potency to achieve targets below 5 mg/dL or 4 mg/dL for faster flare reduction and dissolution of crystal deposition and tophi."