An extended-release formulation, HR091506, performs better than febuxostat immediate release in lowering urate levels in patients with gout and hyperuricaemia, as shown in a phase III trial.
HR091506 is also well tolerated and has an acceptable safety profile, according to lead study author Dr Xue Yu from Huashan Hospital, Fudan University, Shanghai, China.
Adult patients aged 18‒75 years who met the 2015 ACR/EULAR classification criteria for gout, had serum uric acid (SUA) ≥480 μmol/L, and had at least two gout flares in the year prior to screening, tophi, or chronic gouty arthroplasty were enrolled in this multicentre, randomized, double-blind phase III trial.
Of the 442 eligible patients, 221 were randomly allocated to HR091506 and 221 to febuxostat for 36 weeks. Participants in each group received 20 mg once daily during weeks 1 to 4, 40 mg once daily during weeks 5 to 8, 60 mg daily during weeks 9 to 12, and 80 mg once daily during weeks 13 to 36.
At week 36, a significantly greater proportion of patients treated with HR091506 than those treated with febuxostat achieved the primary endpoint of <300 μmol/L (63.8 percent [95 percent confidence interval [CI], 57.5‒70.1] vs 40.7 percent [95 percent CI, 34.2‒47.2]; difference, 22.9 percent, 95 percent CI, 14.2‒31.6; p<0.0001). [EULAR 2026, abstract LB0008]
These findings persisted in almost all prespecified subgroups, with greater benefits seen with HR091506 than with febuxÂostat.
Similarly, significantly more patients in the HR091506 group than in the febuxostat group achieved SUA <360 μmol/L at week 36 (74.2 percent [95 percent CI, 68.4‒80.0] vs 65.6 percent [59.3‒71.9; difference, 8.4 percent, 95 percent CI, 0.1‒16.8; p=0.0466).
“HR091506 also showed higher proportions of patients achieving SUA <300 and <360 μmol/L at all [study] visits,” said Yu.
Safety profile
Treatment with HR091506 vs febuxostat resulted in greater reductions in SUA levels at week 36, with a bigger mean change from baseline (‒309.0 vs ‒267.8 μmol/L) and a higher percentage change from baseline (‒52.04 percent vs ‒44.78 percent).
No significant difference was observed in the overall incidence of treatment-emergent adverse events (TEAEs) between the HR091506 and febuxostat groups (90.5 percent vs 90.0 percent). Likewise, no significant between-group difference was noted in the incidence of treatment-related TEAEs (65.6 percent vs 70.1 percent).
Furthermore, more patients treated with HR091506 experienced serious TEAEs than those who received febuxostat (6.3 percent vs 3.2 percent).
Extended release
HR091506 is a febuxostat oral extended-release formulation developed using gastroretentive drug delivery technology with pulsatile release characteristics. [https://www.vcbeathealth.com/article/45262]
It consists of an immediate-release portion, which rapidly releases in the stomach to quickly achieve effective blood drug concentration, and a sustained release portion, which retains in the stomach and continuously releases, extending xanthine oxidase inhibition time for more sustained urate-lowering effects. [https://www.vcbeathealth.com/article/45262]
“Febuxostat immediate release, a xanthine oxidase inhibitor, is used to manage hyperuricaemia in gout by reducing urate levels,” wrote Yu and colleagues. “HR091506, an extended-release formulation, was developed to prolong drug exposure and reduce urate to target levels.”