Innovent Biologics announced promising Phase 2 results for tigulixostat (IBI128), a next-generation xanthine oxidase inhibitor, demonstrating superior urate-lowering efficacy compared to febuxostat in Chinese gout patients. The results were presented at the 2025 Asia-Pacific League of Associations for Rheumatology (APLAR) Congress, with the company planning to advance to Phase 3 trials in the second half of 2025.
Study Design and Patient Population
The randomized, open-label, multicenter Phase 2 study (NCT06501534) enrolled 84 participants with a mean age of 37 years and mean baseline serum uric acid (sUA) of 575 μmol/L (9.6 mg/dL). Patients were randomized to receive tigulixostat at doses of 50 mg, 100 mg, or 200 mg, or febuxostat 40 mg for 16 weeks (18 weeks for the tigulixostat 200 mg group).
Efficacy Results Show Dose-Dependent Response
Tigulixostat demonstrated significantly greater urate-lowering efficacy across all dose groups with a clear dose-dependent effect. At week 16, the proportion of participants achieving sUA <360 μmol/L (6 mg/dL) was:
- Tigulixostat 50 mg: 55.0% (treatment difference vs febuxostat: 36.8%, 95% CI: 9.7-63.9, P<0.01)
- Tigulixostat 100 mg: 81.0% (treatment difference: 62.8%, 95% CI: 39.5-86.0, P<0.001)
- Tigulixostat 200 mg: 85.7% (treatment difference: 67.5%, 95% CI: 45.5-89.5, P<0.001)
- Febuxostat 40 mg: 18.2%
For the more stringent target of sUA <300 μmol/L (5 mg/dL), tigulixostat showed even more pronounced benefits:
- Tigulixostat 50 mg: 30.0% (treatment difference: 20.9%, P<0.05)
- Tigulixostat 100 mg: 61.9% (treatment difference: 52.8%, P<0.001)
- Tigulixostat 200 mg: 81.0% (treatment difference: 71.9%, P<0.001)
- Febuxostat 40 mg: 9.1%
The percent change in sUA from baseline at week 16 ranged from -38.66% with tigulixostat 50 mg to -57.11% with tigulixostat 200 mg, compared to -24.11% with febuxostat.
Safety Profile Addresses Current Treatment Limitations
Tigulixostat demonstrated a favorable safety profile with no increased risk of renal impairment. The incidence of adverse events was similar across all groups, with all reported adverse events being mild to moderate in severity. Notably, no serious adverse events or adverse events of special interest were observed in any tigulixostat-treated groups, and no adverse events led to study drug discontinuation.
Without gout flare prophylaxis during the study, the incidences of gout flare were comparable between tigulixostat and febuxostat groups. Most gout flares occurred during the initial 4 weeks of treatment, with incidence gradually decreasing thereafter.
Addressing Unmet Medical Need
Professor Hejian Zou from Huashan Hospital affiliated with Fudan University, the study's principal investigator, emphasized the clinical significance: "Gout and hyperuricemia are increasingly becoming the 'fourth major' chronic disease following hypertension, hyperlipidemia, and hyperglycemia. The overall prevalence of hyperuricemia in China is 13.3%, and hyperuricemia is a prerequisite for gout. Among hyperuricemia patients, approximately 15.5 million suffer from gout."
Current treatment options face significant safety concerns. Allopurinol carries a substantial risk of hypersensitivity syndrome in Han Chinese populations, with associated mortality reaching approximately 30%. Meanwhile, long-term febuxostat use is associated with elevated risks of hepatic dysfunction and cardiovascular adverse events.
Development Timeline and Strategic Partnership
Dr. Lei Qian, Chief R&D Officer of General Biomedicine from Innovent Biologics, stated that the company will accelerate Phase 3 clinical development based on these findings and ongoing regulatory communications. Tigulixostat has previously completed Phase 2 studies in the United States and international multicenter Phase 3 trials, consistently demonstrating superior efficacy compared to febuxostat with favorable tolerability.
In December 2022, Innovent Biologics entered a strategic collaboration with LG Chem, securing exclusive development and commercialization rights for tigulixostat in China.
Mechanism and Clinical Potential
Tigulixostat is a next-generation, non-purine selective xanthine oxidase inhibitor that blocks the conversion of hypoxanthine and xanthine to uric acid, thereby reducing uric acid production and lowering serum uric acid levels. The drug's superior efficacy profile, combined with its favorable safety characteristics, positions it as a potential solution to the current treatment limitations in gout management.
