Novel gout therapies demonstrate early promise in recent studies
Presenters: Robert T. Keenan, MD, MPH; Ullrich Schwertschlag, MD, PhD; Yu Xue, MD, PhD
Efficacy of pozdeutinurad (AR882) in treatment naïve and suboptimally treated gouty arthritis with tophi. Abstract 1138. Presented October 27, 2025.
Efficacy and safety of firsekibart in acute gouty arthritis patients with limited treatment options: a multicenter, randomized, double-blind, double-dummy, active-controlled phase III trial. Abstract 2013. Presented October 28, 2025.
Efficacy and safety of firsekibart in acute gouty arthritis patients with eGFR < 60 mL/min/1.73m2: a post-hoc analysis of 24-week data. Abstract 2014. Presented October 28, 2025.
A phase 2a study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ABP-671 in subjects with hyperuricemia or gout in China. Abstract 2012. Presented Oct 28, 2025.
At ACR Convergence 2025, several reports detailed new and investigational therapies that offer the potential to provide additional options for treating gout. Below are meeting highlights based on emerging options that aim to expand the therapeutic landscape, particularly for patients who do not respond to standard treatments.
Pozdeutinurad in gouty arthritis with tophi
A novel selective URAT1 inhibitor, pozdeutinurad, has demonstrated substantial reductions in serum uric acid and high rates of tophus resolution in a recently presented phase 2 study.
Pozdeutinurad is a blocker of urate transporter 1 (URAT1), which plays a key role in the reabsorption of uric acid. The agent is currently in phase 3 studies for the treatment of gout and tophaceous gout.
The current phase 2 study, presented at ACR Convergence 2025, included 42 patients with subcutaneous tophi who either had received no previous treatment or whose gout was suboptimally controlled with available urate-lowering therapy.
In both of these patient subsets, investigators reported, treatment with pozdeutinurad 75 mg produced clinically significant and sustained responses in serum uric acid levels, both as monotherapy and in combination with allopurinol.
“Many times patients who were not at their target uric acid level are expected to continue to be difficult to treat, but with pozdeutinurad, there was no clinically significant difference in uric acid reduction between those who were on urate-lowering therapy previously and those who were not,” said Robert T. Keenan, MD, MPH, of Arthrosi Therapeutics.
The mean uric acid decrease with pozdeutinurad 75 mg alone was 49% in treatment-refractory patients and 54% in previously untreated patients, study results show.
Adding allopurinol to pozdeutinurad 75 mg produced numerically greater uric acid responses, with mean decreases of 61% in patients with refractory gout and 74% in previously untreated patients.
At 12 months, complete resolution of at least 1 target tophus was seen in 43% of patients with refractory gout receiving pozdeutinurad 75 mg alone, and 57% in those receiving pozdeutinurad 75 mg plus allopurinol.
In addition, the treatment-refractory group demonstrated substantial reductions in urate crystal burden, investigators reported.
The investigators concluded that pozdeutinurad, alone or combination, may provide an effective treatment option for patients with chronic tophi and inadequate response to standard urate-lowering therapy.
“As an oral, once-daily therapy, pozdeutinurad may be a great option for those for whom oral therapies fail or who cannot tolerate them, used before intravenous therapies such as pegloticase, and even in those for whom intravenous uricases fail or cannot be tolerated,” Dr. Keenan said.
ABP-671, a selective and potent URAT1 inhibitor
A selective and potent URAT1 inhibitor known as ABP-671 produced dose-dependent reductions in serum uric acid in adults with hyperuricemia or gout, according to results of a phase 2a study conducted in China.
The investigational agent, also known as lingdolinurad, had acceptable safety and tolerability among Chinese participants in the study, which was presented at ACR Convergence 2025 in a poster session by Ullrich Schwertschlag, MD, PhD, of Atom Therapeutics.
The trial included 45 participants randomized to receive daily oral doses of ABP-671 ranging from 1 to 12 mg or placebo.
Serum uric acid levels decreased in a dose-dependent manner, according to data presented at the meeting.
Among the participants with gout, the mean serum uric acid decrease was 56.4% at the lowest dose (1 mg) and 79.2% at the highest dose (12 mg). By contrast, the decrease was just 17.7% in the placebo group.
Similarly, among the participants with hyperuricemia, mean serum uric acid decreases ranged from 50.1% at the lowest dose and 82.1% at the highest dose, with a drop of just 19.9% for placebo.
By contrast, the incidence of adverse events was not found to be dose-dependent, and most adverse events were mild, according to investigators. No serious adverse events or deaths were reported.
Research continues on lingdolinurad/ABP-671. In September, Atom Therapeutics reported that a global phase 2b/3 clinical trial of the oral URAT1 inhibitor achieved its primary efficacy endpoint in lowering serum uric acid levels in patients with chronic gout.
Firsekibart in acute gouty arthritis
In another study, presented at ACR Convergence 2025 by researcher Yu Xue, MD, PhD, the anti-interleukin 1-beta monoclonal antibody firsekibart demonstrated superiority to compound betamethasone in preventing flares among patients with acute gouty arthritis and limited treatment options.
In this multicenter, randomized, double-blind phase 3 study conducted in China, firsekibart (formerly known as genakumab) provided rapid pain relief and significantly superior flare prevention in patients who could not tolerate or did not respond to nonsteroidal anti-inflammatory drugs or colchicine.
In the 313 participants, firsekibart demonstrated better pain relief from 48 hours to 7 days than compound betamethasone, the investigators said.
In addition, firsekibart reduced the risk of a new flare by 90% over 12 weeks, and by 87% over 24 weeks, they reported.
Firsekibart also significantly prolonged the time to first new flares, and fewer firsekibart-treated patients experienced new flares at the 12- and 24-week time points, the data show.
Rates of adverse events were similar between treatment groups, and no serious adverse events were reported in the firsekibart group, the investigators said.
Also reported at ACR Convergence 2025 was a post hoc analysis of 42 participants in the phase 3 trial who had an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2.
In this subset of patients, it was reported that firsekibart relieved pain and prevented new flares as well as it did in the overall study population, with a similar safety profile.
According to the investigators, approximately 70% of adults with gout have chronic kidney disease of stage 3 or greater, defined by an eGFR below 60 mL/min/1.73 m2, a finding that they say significantly restricts standard treatment options because of the potential for renal toxicity.
Disclosures
Robert T. Keenan, MD, MPH, is an employee of Arthrosi Therapeutics. Ullrich Schwertschlag, MD, PhD reported a disclosure (consulting) related to Atom Therapeutics (formerly Atom Bioscience). Yu Xue, MD, PhD, reported no disclosures.
References
Keenan R, Khanna P, Shen Z, et al. Efficacy of pozdeutinurad (AR882) in treatment naïve and suboptimally treated gouty arthritis with tophi [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/efficacy-of-pozdeutinurad-ar882-in-treatment-naive-and-suboptimally-treated-gouty-arthritis-with-tophi/. Accessed October 27, 2025.
Xue Y, Chu T, Hu J, et al. Efficacy and safety of firsekibart in acute gouty arthritis patients with limited treatment options: a multicenter, randomized, double-blind, double-dummy, active-controlled phase III trial [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-firsekibart-in-acute-gouty-arthritis-patients-with-limited-treatment-options-a-multicenter-randomized-double-blind-double-dummy-active-controlled-phase-iii-trial/. Accessed October 27, 2025.
Xue Y, Chu T, Hu J, Gou W, et al. Efficacy and safety of firsekibart in acute gouty arthritis patients with eGFR < 60 mL/min/1.73 m2: a post-hoc analysis of 24-week data [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-firsekibart-in-acute-gouty-arthritis-patients-with-egfr-60ml-min-1-73m2a-post-hoc-analysis-of-24-week-data/. Accessed October 27, 2025.
Schwertschlag U, Yang Y, Li J, et al. A phase 2a study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ABP-671 in subjects with hyperuricemia or gout in China [abstract]. Arthritis Rheumatol 2025; 77 (suppl 9). https://acrabstracts.org/abstract/a-phase-2a-study-to-evaluate-the-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-multiple-ascending-doses-of-abp-671-in-subjects-with-hyperuricemia-or-gout-in-china/. Accessed October 27, 2025.
Atom Therapeutics announces positive topline results of lingdolinurad (ABP-671) in phase 2b/3 trial for chronic gout [press release]. September 8, 2025. https://atomthera.us/2025/09/07/atom-announces-positive-topline-results-of-lingdolinurad-in-phase-2b-3-trial-for-gout/. Accessed October 27, 2025.