Lingdolinurad Demonstrates Dose-Dependent Serum Uric Acid Reductions

Lingdolinurad (ABP-671) had acceptable safety and tolerability and reduced serum uric acid (sUA) in people with hyperuricemia or gout in a new study.1

Findings from a phase 2a study evaluating ligdolinurad were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Ullrich Schwertschlag, MD, PhD, FACP, Atom’s Senior Vice President of Clinical Development.

The study enrolled adult participants up to the age of 55 years without clinically significant kidney abnormalities on renal ultrasound and non-symptomatic hyperuricemia or gout, as evidence by 2 separate fasting sUA results of >7 mg/dL 24 hours apart. Participants were randomized to 5 multiple ascending oral dose groups including 1, 2, 4, 6, 12 mg of ABP-671 and placebo in a 7/2 ratio. The dose escalation dosing period started from 0.2 mg to 1 mg over a 9-day or 10-day period to mitigate any renal sUA overload and was then followed by a 7-day dosing period of ABP-671 or placebo. Investigators enrolled groups separately and conducted them sequentially.

Schwertschlag and colleagues found that treatment-emergent adverse events (TEAEs) were reported in 24 participants (53.3%), including 5 (71.4%), 4 (57.1%), 6 (85.7%), 4 (57.1%), 1 (14.3%), and 4 (40%) in the 1, 2, 4, 6, and 12 mg and placebo groups, respectively. There were no serious AEs, grade >3 TEAEs, or deaths. Notably, investigators did not observe AE incidence to be dose dependent. Participants followed a structured dose-escalation regimen before reaching their assigned target doses. In Group 1, dosing increased from 0.2 mg once daily (QD) on days 1–3 to 0.5 mg QD on days 4–10 and 1 mg QD on days 11–17. Group 2 received 0.2 mg QD on days 1–3, 0.5 mg QD on days 4–6, 1 mg QD on days 7–9, and 2 mg QD on days 10–16. Groups 3, 4, and 5 escalated to target doses of 4 mg, 6 mg, and 12 mg QD, respectively, administered from days 10–16.1

The investigators found that sUA levels decreased in a dose dependent manner, with the max median decreases of sUA occurring at 3.00-9.00 hours post dose. Serum uric acid (sUA) levels declined in a clear dose-dependent manner, with the greatest median reductions observed between 3 and 9 hours postdose. Among participants with gout, maximum mean sUA decreases from baseline were 17.7% with placebo, 56.4% with 1 mg, 58.1% with 2 mg, 69.4% with 4 mg, 77.0% with 6 mg, and 79.2% with 12 mg. In participants with hyperuricemia, corresponding reductions were 19.9%, 50.1%, 64.1%, 73.2%, 81.2%, and 82.1%.1

At 24 hours postdose, the proportion of participants reaching sUA thresholds <6.0 mg/dL, <5.0 mg/dL, and <4.0 mg/dL increased consistently with dose. For the 1-mg group, rates were 85.7%, 57.1%, and 14.3%, respectively; for 2 mg, 100%, 85.7%, and 14.3%; for 4 mg, 100%, 85.7%, and 14.3%; for 6 mg, 100%, 100%, and 57.1%; and for 12 mg, 100%, 100%, and 100%. No placebo recipients achieved any of these sUA thresholds.1

Atom also presented phase 1 safety and pharmacokinetic data on its novel colchicine analogue ABP-745 at the ACR conference in healthy volunteers that demonstrated the drug was well-tolerated and exhibited dose proportional pharmacokinetics. Atom recently also enrolled the first patient in a multicenter Phase 2 acute gout flare trial that will compare ABP-745 with placebo and colchicine.2

“The positive findings in both of these studies have contributed to successfully advancing our goal of providing meaningful relief to patients worldwide suffering from the damaging effects of chronic gout and the disease’s painful acute gout flares,” William Dongfang Shi, PhD, Founder and CEO of Atom, said.2 “Both ABP-671 and ABP-745 have the potential to give gout patients more effective and safer alternatives to existing gout therapies, which have insufficient efficacy and are often associated with serious or even life-threatening adverse effects.”

References

1. Schwertschlag U, Yang Y, Li J, et al. A Phase 2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of ABP-671 in Subjects with Hyperuricemia or Gout in China. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #2012

2. Atom Therapeutics to Present Positive Data from Clinical Trials of Its Lead Novel Oral Drugs for Chronic Gout and Acute Gout Flares at ACR Convergence 2025. News release. Atom Therapeutics. October 21, 2025. https://aijourn.com/atom-therapeutics-to-present-positive-data-from-clinical-trials-of-its-lead-novel-oral-drugs-for-chronic-gout-and-acute-gout-flares-at-acr-convergence-2025/