A novel compound emerging as a treatment for refractory gout

SAP-001, a first-in-class urate-lowering therapy, successfully reduced serum urate (sUA) levels to ≤6 mg/dL in 43.8% to 70% of participants, depending on the dosing regimen. However, a clear dose-response relationship, the primary endpoint, was not met.

“Given the high prevalence of gout and the limited number of therapeutic options, a high unmet need remains for novel urate-lowering therapies with both excellent efficacy and low toxicity,” stated Prof. Kenneth G. Saag (University of Alabama at Birmingham, AL, USA). SAP-001 is a novel compound targeting a major renal urate reabsorption transporter distinct from URAT1.

Prof. Saag presented phase 2 data on SAP-001 (NCT05690204) [1]. Eligible participants were adults with refractory gout and sUA levels ≥7 mg/dL. Following a placebo run-in phase, participants were treated either with placebo or SAP-001 at doses of 10 mg, 30 mg, or 60 mg, over 85 days, at which point the primary endpoint of the proportion of participants with sUA ≤6 mg/dL was evaluated. Treatment continued until day 169.

Across the study arms, participants were predominantly male (87.5%–96.9%), with a mean age between 50.3 and 55.9 years. All had a body mass index >30 kg/m2 and preserved kidney function. The mean baseline sUA levels were 8.37 mg/dL.

At all study time points, a significant reduction in sUA levels and a higher proportion of participants meeting the primary endpoint were observed in the active arms compared with placebo. The proportion of participants achieving target sUA levels was 56.3% in the 10 mg arm, 70.0% in the 30 mg arm, and 43.8% in the 60 mg arm, compared with 10.5% in the placebo group. A statistically significant dose-response relationship was not established (P=0.148). Assessing the percentage of participants achieving sUA ≤5 mg/dL, Prof. Saag mentioned efficacy rates between about 40% and 60% in the different groups (see Figure).

Figure: Proportion of participants achieving sUA <5 mg/dL in the different study arms [1]



QD, once daily.

Adverse events of special interest, which included transient creatine elevations or decreased glomerular filtration rate, were few (15 events in 11 participants), with a numerically higher incidence in the SAP-001 arms. All were mild or moderate and non-serious. Gout flares occurred in 26.3% of participants on placebo and 25%–30% of those receiving SAP-001.

“SAP-001 demonstrated sustained urate-lowering effects in patients with refractory gout, with or without tophi,” Prof. Saag summarised. He concluded that the drug may offer a novel, efficacious, and safe treatment option for patients with difficult-to-treat gout.

1. Saag KG, et al. SAP-001, A first-in-class compound targeting a renal urate transporter, shows potent serum urate-lowering effects and favourable safety profile in a US phase 2b study in patients with refractory gout with or without palpable LB0008, EULAR 2025, 11–14 June, Barcelona, Spain.

Copyright ©2025 Medicom Medical Publishers



Posted on 8 August 20252 September 2025