POS0268 AR882, A NOVEL AND SELECTIVE URAT1 INHIBITOR, SIGNIFICANTLY REDUCED TOPHI IN PATIENTS WITH CHRONIC GOUTY ARTHRITIS: RESULTS OF 12-MONTH OUTCOME FROM A GLOBAL TRIAL USING DIGITAL CALIPER MEASUREMENTS AND DUAL ENERGY COMPUTED TOMOGRAPHY

Background:

AR882 is a novel and selective URAT1 inhibitor currently in clinical stage development for the treatment of gout and tophaceous gout. In the first 6-month period of a phase 2 proof-of-concept trial in patients with chronic gouty arthritis, AR882 has demonstrated significant reduction in serum urate (sUA) and marked reduction of clinically visible subcutaneous tophi and total urate crystal deposition by digital caliper measurement and Dual Energy Computer Tomography (DECT), respectively.

Objectives:

To evaluate the long-term effect of AR882 on the resolution of target subcutaneous tophi and reduction in urate crystal deposition volume using DECT in gout patients with subcutaneous tophi.

Methods:

The phase 2, randomized, open-label, global trial, recruited 42 patients with at least one subcutaneous tophus. The patients were randomized equally into three treatment groups to receive AR882 75 mg once daily (QD), AR882 50 mg + allopurinol QD, or allopurinol up to 300 mg QD. At 6 months all participants were eligible to enroll in a 6-month extension. Those in the allopurinol monotherapy group who opted in the 6-month extension had AR882 75 mg added to their current allopurinol regimen (AR882 75 mg + allopurinol QD), while patients in other groups continued their current regimen. Tophi measurements with calipers were completed every 4 weeks for the first 6 months followed by every 3 months in the extension phase. DECT imaging was conducted at baseline, Months 6 and 12. Efficacy endpoints included change in sUA change from baseline and change from baseline in target tophus area and crystal volume at Months 6 and 12. Safety assessments, including vital signs and electrocardiograms, were collected throughout the study.

Results:

The average baseline sUA level ranged between 9.1-9.6 mg/dL across groups. At Month 3, the median sUA levels were reduced to 4.5, 4.7, and 6.1 mg/dL for AR882 75 mg, AR882 50 mg+allopurinol and allopurinol groups, respectively. At Month 12, sUA levels were 4.3 mg/dL, 3.7 mg/dL and 2.9 mg/dL for AR882 75 mg, AR882 50 mg+allopurinol and AR882 75 mg+allopurinol groups, respectively. At Month 6, complete tophus resolution of at least 1 target tophus measured by digital caliper was seen with 4 patients (29%) in the AR882 75 mg group, 1 patient (8%) in allopurinol and 1 patient (8%) in AR882 50 mg + allopurinol group. During the 6 months extension phase, complete tophus resolution was seen in 5 patients (50.0%) and 4 patients (36.4%) in the AR882 75 mg and AR882 75 mg+allopurinol groups, respectively (Table 1). The AR882 75 mg alone or combined with allopurinol showed reduction of total urate crystal volume from baseline to Month 6 with sustained crystal volume reduction through Months 6 to 12. AR882 was well tolerated throughout 12-month chronic treatment as monotherapy or in combination with allopurinol. The most frequently reported adverse event was gout flare, mild or moderate adverse events including diarrhea, headache, and upper respiratory infection. Gout flare rate appeared continued to decline following AR882 treatment.

Conclusion:

The 12-month treatment of AR882 in patients with tophaceous gout demonstrated safe and efficacious sUA lowering, continued tophus resolution and total crystal volume dissolution from initial 6-month treatment. AR882 may offer improved efficacy and better safety compared to existing therapies in the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests:

Robert Keenan Arthrosi Therapeutics Inc, James Cheng-Chung Wei Arthrosi Therapeutics Inc, Nicola Dalbeth AstraZeneca, Novartis, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, and Dexcel Pharma., AstraZeneca, Novartis, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, and Dexcel Pharma., AstraZeneca, Novartis, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, and Dexcel Pharma., Sarah Morris Arthrosi Therapeutics Inc, Pamela Mundell Arthrosi Therapeutics Inc, Wen Wei Arthrosi Therapeutics Inc, Zancong Shen Arthrosi Therapeutics Inc, Vijay Hingorani Arthrosi Therapeutics Inc, Shunqi Yan Arthrosi Therapeutics Inc, Bahram Kiani: None declared, Li-Tain Yeh Arthrosi Therapeutics Inc.