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LONDON — An extended-release formulation of the xanthine oxidase inhibitor febuxostat was significantly better at lowering uric acid than standard immediate-release febuxostat in patients with hyperuricemia and chronic gout, according to new data from a phase 3 trial presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting. 

Standard immediate-release febuxostat is widely used to manage hyperuricemia by inhibiting xanthine oxidase, thereby lowering urate production. However, standard immediate-release febuxostat clears from the body relatively quickly, causing a peak-and-valley effect whereby drug levels drop, allowing uric acid production to rebound before the next daily dose, said first author and presenter of the study Yu Xue, MD, a rheumatologist and deputy director of the Department of Rheumatology and Immunology at Huashan Hospital, Fudan University, Shanghai, China.

In severe or chronic cases, this temporary drop-off in drug levels is easily overwhelmed by the body's continuous production of uric acid and the constant leaching of old urate deposits out of joints back into the bloodstream.

HR091506 was engineered as an extended-release tablet to prolong systemic drug exposure, potentially maximizing the duration of urate-lowering activity over a 24-hour cycle. “Achieving steady and deep urate reduction is the core of long-term gout management, which aims to dissolve deposited MSU crystals, eliminate tophi, prevent recurrence, and avoid joint and renal damage,” she said.

The Study 

In this multicenter, phase 3 trial, 442 patients aged 18-75 years were enrolled. Participants had high baseline disease severity, defined by serum uric acid (sUA) levels ≥ 480 μmol/L (≥ 8 mg/dL) and a history of at least two gout flares in the preceding year, visible tophi, or chronic gouty arthropathy.

Participants were randomized 1:1 to receive HR091506 (n = 221) or immediate-release febuxostat (n = 221) for 36 weeks. To minimize acute flare risks and ensure dose optimization, both groups underwent an identical gradual titration schedule: 20 mg once daily (weeks 1-4), 40 mg once daily (weeks 5-8), 60 mg once daily (weeks 9-12), and a maintenance dose of 80 mg once daily (weeks 13-36).

Significant Clearance and Deep Reductions of sUA

The extended-release formulation demonstrated clear statistical superiority over the standard regimen in the proportion of patients who met the trial’s primary endpoint of sUA levels < 300 μmol/L (< 5 mg/dL) at week 36 (about 64% with HR091506 vs about 41% in the immediate-release group).

In addition, the average depth of urate reduction from baseline to week 36 was substantially greater with HR091506 than standard treatment. Patients taking the extended-release formulation experienced a mean absolute reduction in sUA of -309.0 μmol/L (-5.19 mg/dL; 52.0% reduction), compared with -267.8 μmol/L (-4.47 mg/dL; 44.8% reduction) in the standard arm.

Safety Profile

Treatment-emergent adverse events, such as stomach issues or headaches, affected about 90% of patients in both groups. However, serious adverse events occurred in 6.3% of patients taking the new long-acting formula, double the 3.2% rate seen in the standard group. “I’d be interested in whether there might be a similar increased risk of cardiovascular events with the sustained release [to what is seen] with the immediate release,” Jonathan Kay, MD, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts School of Medicine, Worcester, told Medscape Medical News.

Despite the increase, Xue said that treatment-related serious side effects remained minimal, and no deaths occurred in either group. She concluded that the new drug's safety profile is acceptable relative to its robust performance. Because the extended-release formulation is so much better at clearing out the uric acid that causes painful joint damage, it may be a new tool for people struggling with severe, hard-to-treat gout, she said.

The trial was sponsored by Jiangsu Hengrui Pharmaceuticals. Xue has reported no relevant financial relationships. Two coauthors are employees of Jiangsu Hengrui Pharmaceuticals. Kay is a consultant to Artiva Biotherapeutics, AstraZeneca, Cue Biopharma, Immunovant, Immunitas Therapeutics, Organon, Samsung Bioepis, and Spyre Therapeutics.

Manuela Callari is a freelance science journalist specializing in human and planetary health. Her work has been published in The Medical Republic, Rare Disease Advisor, New Scientist, The Guardian, MIT Technology Review, and others.