OP0300 SAFETY AND TOLERABILITY OF POZDEUTINURAD (AR882) TREATMENT FOLLOWING LONG-TERM DOSING IN PATIENTS WITH CHRONIC GOUTY ARTHRITIS AND SUBCUTANEOUS TOPHI

Abstract

Background:

Pozdeutinurad (AR882), a novel and selective URAT1 inhibitor, has demonstrated significant sustained reduction in serum urate (sUA), marked reduction in both clinically visible subcutaneous tophi measured by digital caliper, and total urate crystal deposition measured by Dual Energy Computer Tomography (DECT) in chronic gouty arthritis patients with tophi.

Objectives:

Here we report the long-term safety and tolerability of pozdeutinurad alone or in combination with allopurinol in gout patients with subcutaneous tophi.

Methods:

The phase 2 open-label global trial over 18 months recruited 42 patients with at least one subcutaneous tophus. The patients were randomized equally in three treatment groups to receive pozdeutinurad 75 mg once daily (QD), pozdeutinurad 50 mg + allopurinol QD, or allopurinol up to 300 mg QD in the first 6 months (core phase). At 6 months all patients were eligible to enroll in two 6-month extension phases. The allopurinol monotherapy group who opted for the 6-month extension, had AR882 75 mg added to their current regimen. The arm with pozdeutinurad 50 mg + allopurinol group who opted in the 2nd extension were switched to the pozdeutinurad 75 mg + allopurinol. Efficacy endpoints included change in sUA from baseline and resolution of target tophus. Safety assessments, including vital signs, electrocardiograms, and blood chemistry tests were collected throughout the study.

Results:

During the entire treatment period most treatment-emergent adverse events (TEAE) were mild or moderate in severity. The total number of reported TEAEs was highest during the core phase, and generally decreased throughout the extension phases. The most-frequently-occurring TEAE are provided in Table 1. Gout flare, as expected – was the most frequent adverse events observed in the core phase, with a decreasing trend in the subsequent periods. There were 4 serious adverse events (3 patients) reported, but none of them were considered related to pozdeutinurad, allopurinol, or therapy for flare prophylaxis, such as colchicine. There were no serum creatinine elevations (≥ 1.5X baseline) observed from a total of 478 post-dose measurements in patients receiving either pozdeutinurad or allopurinol up to 18 months (Table 2). Pozdeutinurad alone showed no clinically significant liver function abnormalities (elevation in ALT/AST). Two patients, one with and one without a history of nephrolithiasis, were found to have a renal stone in the first extension phase. These symptoms were considered mild to moderate, did not require treatment, and both completed the study with no or only brief interruption of therapy.

Conclusion:

The long-term treatment of pozdeutinurad alone or in combination with allopurinol for the treatment of tophaceous gout patients was well tolerated, showed comparable safety profile, and better efficacy to allopurinol alone. These results support pozdeutinurad as a safe option for the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition.

REFERENCES:

NIL. Table 1Most frequently-occurring (≥ 2 patients in any treatment group) treatment-emergent adverse events within 18 months of treatmentCore Phase (6 mo)First Extension (6 mo)Second Extension (6 mo)G1G2G3G1G2G3G1G2Preferred TermALLO(N=13)AR75(N=14)AR50 + ALLO(N=13)AR75 + ALLO(N=12)AR75(N=10)AR50 + ALLO(N=8)AR75 + ALLO(N=16)AR75(N=6)Arthralgia3 (23.1%)4 (28.6%)1 (7.7%)0001 (6.3%)1 (16.7%)Back pain02 (14.3%)00001 (6.3%)1 (16.7%)COVID-1903 (21.4%)000000Diarrhea002 (15.4%)00000Dizziness02 (14.3%)000000Gout flare12 (92.3%)11 (78.6%)8 (61.5%)8 (66.7%)7 (70.0%)4 (50.0%)5 (31.3%)3 (50.0%)Hypertension01 (7.1%)2 (15.4%)00000Joint stiffness1 (7.7%)1 (7.1%)2 (15.4%)00000Nephrolithiasis00002 (20.0%)000Pain in extremity1 (7.7%)1 (7.1%)1 (7.7%)0001 (6.3%)2 (33.3%)Upper respiratory tract infection00002 (20.0%)000Urinary tract infection00002 (20.0%)000AR50: pozdeutinurad (AR882) 50 mg; AR75: pozdeutinurad (AR882) 75 mg; ALLO: allopurinol; mo: month Table 2Elevations of serum creatine or liver functions within 18 months of treatmentCore Phase (6 mo)First Extension (6 mo)Second Extension (6 mo)G1G2G3G1G2G3G1G2Preferred TermALLO(N=13)AR75(N=14)AR50 + ALLO(N=13)AR75 + ALLO(N=12)AR75(N=10)AR50 + ALLO(N=8)AR75 + ALLO(N=16)AR75(N=6)Serum Creatinine# postdose measurements9189916051523212≥1.5X baseline00000000≥2.0X baseline00000000≥3.0X baseline00000000ALT# postdose measurements9192855952513212≥2.0X baseline4 (30.8%)1 (7.1%)05 (41.7%)1 (10.0%)02 (12.5%)0≥3.0X baseline1 (7.7%)001 (8.3%)1 (10.0%)000≥5.0X baseline0000001 (6.3%)0AST# postdose measurements9192855952513212≥2.0X baseline4 (30.8%)01 (7.7%)4 (33.3%)1 (10.0%)02 (12.5%)0≥3.0X baseline0002 (16.7%)001 (6.3%)0≥5.0X baseline00000000AR50: pozdeutinurad (AR882) 50 mg; AR75: pozdeutinurad (AR882) 75 mg; ALLO: allopurinol; mo: month

Acknowledgements:

NIL.

Disclosure of Interests:

Puja Khanna Olatec, Horizon Therapeutics and Arthrosi Therapeutics, Robert Keenan Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Vijay Hingorani Arthrosi Therapeutics Inc, Zancong Shen Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Sarah Morris Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Elizabeth Polvent Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Wen Wei Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Pamela Mundell Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Shunqi Yan Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc, Li-Tain Yeh Arthrosi Therapeutics Inc, Arthrosi Therapeutics Inc. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.