Tigulixostat was successfully tested in patients with gout and hyperuricemia for its serum urate-lowering capacity. The drug was overall well tolerated and without particular safety signals. These results support dose finding and continued development of tigulixostat.
Gout can be effectively managed by inhibiting synthesis of uric acid. In a phase II study (NCT03934099), the novel xanthine oxidase inhibitor tigulixostat was investigated for safety and efficacy in patients with gout and hyperuricemia.1 The study population consisted of 156 patients with gout, who were randomized to receive either placebo or tigulixostat at dosages of 50 mg, 100 mg, or 200 mg daily over 12 weeks followed by an additional 2-week safety follow-up.
Participants had to have a serum urate level greater than 6.0 mg/dL if on prior urate-lowering treatment and a value between 8.0 mg/dL and 12.0 mg/dL after a washout period, or if untreated before. Colchicine 0.6 mg was given as gout flare prophylaxis. “The primary endpoint was subjects achieving serum urates less than 5.0 mg/dL at week 12, as this target is recommended for severe disease including tophaceous gout,” stated Prof. Robert Terkeltaub (Veterans Administration and University of California San Diego). The baseline characteristics of the study population included a mean age of 54, predominantly male patients, and a mean BMI slightly above 30 kg/m2. Prof. Terkeltaub also noted that about 20% had palpable tophi, and most pre-dosing serum urate levels were less than 9.8 mg/dL.
At week 12, 47.1% (50 mg), 44.7% (100 mg), and 62.2% (200 mg) of those on the study drug achieved a serum urate less than 5.0 mg/dL, compared with 2.9% on placebo (P<0.0001 for all dosages). The rate of patients reaching the secondary endpoint of serum urate less than 6.0 mg/dL was also significantly higher when on the study drug, with corresponding proportions of 58.8%, 63.2% and 78.4% versus 2.9%, respectively (P<0.0001). In a small active control group of 13 patients receiving febuxostat, 23% reached serum urate values less than 5.0 mg/dL.
As for safety, 50,0% to 56.8% on tigulixostat and 50.0% on placebo were affected by treatment-emergent adverse events, the majority of mild to moderate severity; four patients discontinued the study due to adverse events. Between 10.8% and 13.2% of tigulixostat patients and 9.4% of placebo patients experienced a gout flare that required rescue treatment.
“In conclusion, tigulixostat significantly lowered serum urate in gout patients, impressively achieved urate targets, and was well tolerated collectively. These results support its continued development for gout with uncontrolled hyperuricemia,” Prof. Terkeltaub stated.
- Terkeltaub R. Phase 2 study results from a randomized, double-blind, placebo-controlled, dose-finding study to evaluate efficacy and safety of tigulixostat, a novel non-purine selective xanthine oxidase inhibitor in gout patients with hyperuricemia. Abstract L05, ACR Convergence 2021, 3– November.
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