Tigulixostat Proves Superiority to Febuxostat in Patients with Gout and Hyperuricemia

Tigulixostat, a xanthine oxidase inhibitor developed by Innovent Biologics, Inc., has demonstrated substantially greater urate-lowering efficacy compared to febuxostat across all dose groups in a phase 2 trial including patients with gout and hyperuricemia.1

Gout is the most common form of inflammatory arthritis, characterized by hyperuricemia and defined by a serum urate concentration ≥6.8 mg/dL, which leads to the formation and deposition of proinflammatory monosodium urate monohydrate crystals in joints and soft tissues. Gout is generally characterized by acute episodes of joint inflammation interspersed with symptom-free periods. Without adequate treatment, gout can lead to serious joint damage and palpable tophi, which can in turn lead to chronic pain and reduced physical function.2

“Gout and hyperuricemia are increasingly becoming the ‘fourth major’ chronic disease following hypertension, hyperlipidemia, and hyperglycemia,” Hejian Zou, MD, Huashan Hospital, said in a statement. “Currently, commonly used clinical drugs for gout in China face safety concerns, including potential cardiovascular risks and hepatorenal toxicity, highlighting the urgen need for safer and more effective treatment options.”1

The trial in question was a randomized, open-label, multicenter, parallel-group, active-controlled phase 2 clinical study aiming to evaluate the efficacy and safety of different tigulixostat doses in patients with gout. A total of 84 participants were included, with a mean age of 37 years, a mean baseline serum uric acid (sUA) of 575 µmol/L, and a mean baseline weight of 80.7 kg. These patients were randomly assigned to either tigulixostat 50 mg, 100 mg, or 200 mg, or febuxostat 40 mg. All dose intervals lasted 16 weeks save for the 200 mg tigulixostat, which lasted 18 weeks.1

By week 16, investigators found a total of 55% of patients in the 50 mg group, 81% in the 100 mg group, and 85.7% in the 200 mg group who had achieved sUA <360 µmol/L, respectively, compared with 18.2% in the febuxostat group. The treatment difference versus febuxostat was 36.8% (95% CI, 9.7 to 63.9; P <.01), 62.8% (95% CI, 39.5 to 86; P <.001), and 67.5% (95% CI, 45.5 to 19.5; P <.001) for the 50 mg, 100 mg, and 200 mg groups, respectively.1

At week 16, 30% of patients in the tigulixostat 50 mg group, 61.9% in the 100 mg group, and 81% in the 200 mg group achieved sUA <300 µmol/L, respectively, versus 9.1% in the febuxostat group. The treatment difference was 20.9% (95% CI, -2.5 to 44.3; P <.05), 52.8% (95% CI, 28.8 to 76.8; P <.001), and 71.9% (95% CI, 51.2 to 92.5; P <.001) for the 50 mg, 100 mg, and 200 mg groups, respectively. Additionally, percent sUA changes from baseline were -38.66% in the 50 mg group, -48.61% in the 100 mg group, 57.11% in the 200 mg group, and 24.11% in the febuxostat group.1

Throughout the trial, tigulixostat also demonstrated a favorable safety profile, showing no increased risk of renal impairment. The incidence of adverse events was also similar across groups.1

“I am delighted to see these results presented at an international academic conference and look forward to tigulixostat entering registered clinical development soon, in hopes that this development can lead to new treatment options for gout patients,” Zou said.1

Innovent Biologics plans to initiate the phase 3 clinical study of tigulixostat in the second half of 2025.1

References

1. Innovent Biologics, Inc. Innovent Announces Phase 2 Results of Tigulixostat (IBI128, XOI) in Gout Patients were Published at the 27th Asia-Pacific League of Associations for Rheumatology Congress. PRNewswire. September 7, 2025. Accessed September 16, 2025. https://www.prnewswire.com/news-releases/innovent-announces-phase-2-results-of-tigulixostat-ibi128-xoi-in-gout-patients-were-published-at-the-27th-asia-pacific-league-of-associations-for-rheumatology-congress-302548517.html

2. Terkeltaub R, Lee J, Min J, Shin S, Saag KG. Serum Urate-Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Trial. Arthritis Rheumatol. 2023;75(7):1275-1284. doi:10.1002/art.42447