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

A total of 84 participants (mean age: 37 years; mean baseline serum uric acid [sUA]: 575 μmol/L [9.6 mg/dL]; mean baseline weight: 80.7 kg) were enrolled and randomized to receive tigulixostat 50 mg, 100 mg, 200 mg or febuxostat 40 mg for 16 weeks (or 18 weeks for the tigulixostat 200 mg group). The primary endpoint was the proportion of participants achieving sUA <360 μmol/L (6 mg/dL) at Week 16.

Tigulixostat demonstrated significantly greater urate-lowering efficacy compared to febuxostat across all dose groups, with a dose-dependent effect.

• At week 16, 55.0% of participants in the tigulixostat 50 mg group, 81.0% in the tigulixostat 100 mg group, and 85.7% in the tigulixostat 200 mg group, achieved sUA <360 μmol/L (6 mg/dL), respectively, compared with 18.2% in the febuxostat 40 mg group, the treatment difference versus febuxostat was 36.8% (95%CI: 9.7, 63.9, P<0.01), 62.8% (39.5, 86.0, P<0.001), and 67.5% (45.5, 89.5, P<0.001) for the tigulixostat 50 mg group, 100 mg group, and 200 mg group, respectively;
• At week 16, 30.0% of participants in the tigulixostat 50 mg group, 61.9% in the tigulixostat 100 mg group, and 81.0% in the tigulixostat 200 mg group, achieved sUA <300 μmol/L (5 mg/dL), respectively, compared with 9.1% in the febuxostat 40 mg group, the treatment difference versus febuxostat was 20.9% (95%CI: –2.5, 44.3, P<0.05), 52.8% (28.8, 76.8, P<0.001), and 71.9% (51.2, 92.5, P<0.001) for the tigulixostat 50 mg group, 100 mg group, and 200 mg group, respectively.
• At week 16, the percent change in sUA from baseline were -38.66% in the tigulixostat 50 mg group, -48.61% in the tigulixostat 100 mg group、-57.11% in the tigulixostat 200 mg group, and -24.11%（in the febuxostat 40 mg group.
• Tigulixostat demonstrated a favorable safety profile, no increased risk of renal impairment. The incidence of adverse events was similar across groups. All reported AEs were mild to moderate in severity. No serious adverse events or adverse events of special interest were observed in any tigulixostat -treated groups. No adverse events led to temporary or permanent discontinuation of the study drug was observed.
• Without any gout flare prophylaxis during the study, the incidences of gout flare were comparable between the tigulixostat total group and the febuxostat 40 mg group. Most gout flare occurred during the initial 4 weeks of treatment, with the incidence gradually decreasing and reaching a plateau subsequently. It has been reported that higher and more sustained serum uric acid target achievement can significantly reduce the risk of gout flare^[1].

The Principal Investigator of the Study, Professor Hejian Zou from Huashan Hospital affiliated with Fudan University, stated: "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. Gout patients face an increased risk of cardiovascular diseases and chronic kidney diseases, and it is also closely associated with comorbidities such as diabetes and stroke, often leading to significantly elevated mortality risks. Currently, commonly used clinical drugs for gout in China face safety concerns, including potential cardiovascular risks and hepatorenal toxicity, highlighting the urgent need for safer and more effective treatment options. Tigulixostat is a novel non-selective XO inhibitor, and the Phase 2 clinical study results in Chinese gout participants have fully demonstrated its significantly urate-lowering efficacy with a good safety profile. I am delighted to see these results presented at an international academic conference and look forward to that tigulixostat entering registered clinical development soon, in hopes that this development can lead to new treatment options for gout patients in China."

Dr. Lei Qian, Chief R&D Officer of General Biomedicine from Innovent Biologics, stated, "We are delighted to present the Phase 2 clinical study results of tigulixostat at the international academic congress. The study demonstrated tigulixostat's superior urate-lowering efficacy compared to febuxostat, while maintaining a favorable safety profile across multiple dose levels in Chinese gout participants. Building on these findings and through ongoing communication with regulatory authorities, we will accelerate the Phase 3 clinical development of tigulixostat to bring this promising treatment option to Chinese gout patients as soon as possible. As part of our commitment, Innovent Biologics will continue to advance our next-generation pipeline in cardiovascular and metabolic diseases, targeting the broad population affected by hypertension, hyperlipidemia, hyperglycemia, and hyperuricemia. We remain dedicated to fulfilling patients' aspirations for healthier lives and expanding access to innovative therapies."

About Gout

Gout is an inflammatory arthritis caused by the gradual elevation of uric acid levels in the blood, exceeding its solubility threshold^[2], leading to the deposition of monosodium urate (MSU) crystals in joints. Persistent hyperuricemia can result in the accumulation of urate crystals (tophi) in joints, tendons, and other tissues, which, under triggering factors (e.g., trauma, cold exposure, inflammatory stimuli), may provoke acute inflammatory episodes known as acute gout attacks.

Hyperuricemia is a metabolic disorder syndrome resulting from purine metabolism dysfunction. It is defined as serum uric acid levels exceeding 420 μmol/L on two separate occasions, regardless of gender. Hyperuricemia and gout represent a continuous, chronic pathophysiological spectrum and constitute a systemic disease affecting multiple organ systems. The prevalence of hyperuricemia varies across ethnicities, ranging from 2.6% to 36%, while gout prevalence ranges from 0.03% to 15.3% globally^[3].

The most widely prescribed urate-lowering drugs in China are xanthine oxidase (XO) inhibitors: allopurinol and febuxostat. However, allopurinol carries a significant risk of hypersensitivity syndrome in Han Chinese populations, with associated mortality reaching approximately 30%. This safety concern has substantially restricted its clinical utility. Meanwhile, long-term febuxostat use demonstrates associations with elevated risks of hepatic dysfunction and cardiovascular adverse events^[4-7]. These limitations underscore the urgent need for novel therapeutic agents with improved safety profiles and enhanced efficacy in hyperuricemia management.

About Tigulixostat (IBI128)

Tigulixostat (IBI128) is a next-generation, non-purine selective xanthine oxidase inhibitor (XOI). It exerts its therapeutic effect by inhibiting xanthine oxidase activity, thereby blocking the conversion of hypoxanthine and xanthine to uric acid. This mechanism reduces uric acid production and subsequently lowers serum uric acid levels, making it an effective treatment for hyperuricemia in gout patients.

Currently, tigulixostat has completed a Phase 2 clinical study in the United States, an international multicenter Phase 3 clinical study, and Phase 1 and Phase 2 clinical studies in China. The collective data demonstrate that tigulixostat significantly reduces serum uric acid levels and improves urate-lowering target achievement rates in a dose-dependent manner, with superior efficacy compared to febuxostat. Tigulixostat exhibited favorable tolerability across all dose groups, with no observed dose-dependent adverse events.

In December 2022, Innovent Biologics entered a strategic collaboration with LG Chem, securing exclusive development and commercialization rights for tigulixostat in China.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 16 products in the market. It has 2 new drug applications under regulatory review, 4 assets in Phase 3 or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

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