Lingdolinurad Shows Promise in Lowering Uric Acid Levels in Gout and Hyperuricemia Patients
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A new study indicates that lingdolinurad (ABP-671) demonstrates both acceptable safety and tolerability while effectively reducing serum uric acid (sUA) levels in individuals with hyperuricemia or gout. The findings, presented at the American College of Rheumatology (ACR) Convergence 2025 conference held October 24–29 in Chicago, Illinois, offer a potential new avenue for managing these debilitating conditions.
Promising Phase 2a Trial Results
The phase 2a study, led by Ullrich Schwertschlag, MD, PhD, FACP, Atom’s Senior Vice President of Clinical Development, enrolled adult participants up to 55 years of age who exhibited no significant kidney abnormalities and had elevated sUA levels – specifically, readings exceeding 7 mg/dL on two separate fasting tests 24 hours apart. Participants were randomly assigned to receive varying doses of ABP-671 (1, 2, 4, 6, or 12 mg) or a placebo, in a 7/2 ratio. A carefully structured dose escalation period, starting at 0.2 mg and increasing to 1 mg over 9-10 days, was implemented to minimize potential kidney-related complications from sUA overload, followed by a 7-day dosing period with the assigned treatment.
Safety and Tolerability Profile
According to study data, treatment-emergent adverse events (TEAEs) were reported in 53.3% of participants (24 individuals) across all active treatment groups. The incidence rates were 71.4% in the 1 mg group, 57.1% in the 2 mg and 4 mg groups, 85.7% in the 6 mg group, 14.3% in the 12 mg group, and 40% in the placebo group. Importantly, no serious adverse events, grade 3 or higher TEAEs, or deaths were observed. Investigators noted that the incidence of adverse events did not appear to be directly correlated with the dosage administered.
Significant Reduction in Serum Uric Acid
The study revealed a clear dose-dependent reduction in sUA levels, with the most substantial decreases occurring between 3 and 9 hours after administration. Among participants with gout, the maximum mean sUA reductions 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. Individuals with hyperuricemia experienced corresponding reductions of 19.9%, 50.1%, 64.1%, 73.2%, 81.2%, and 82.1%, respectively.
At 24 hours post-dose, a higher proportion of participants achieved clinically relevant sUA thresholds as the dose increased. Specifically:
- 1 mg group: 85.7% reached sUA < 6.0 mg/dL, 57.1% < 5.0 mg/dL, and 14.3% < 4.0 mg/dL.
- 2 mg group: 100% reached sUA < 6.0 mg/dL, 85.7% < 5.0 mg/dL, and 14.3% < 4.0 mg/dL.
- 4 mg group: 100% reached sUA < 6.0 mg/dL, 85.7% < 5.0 mg/dL, and 14.3% < 4.0 mg/dL.
- 6 mg group: 100% reached sUA < 6.0 mg/dL and < 5.0 mg/dL, and 57.1% < 4.0 mg/dL.
- 12 mg group: 100% reached all three thresholds (< 6.0 mg/dL, < 5.0 mg/dL, and < 4.0 mg/dL).
Notably, no participants in the placebo group achieved any of these sUA targets.
Additional Research on ABP-745
Atom Therapeutics also presented positive phase 1 data on its novel colchicine analogue, ABP-745, demonstrating good tolerability and dose-proportional pharmacokinetics in healthy volunteers. Furthermore, the company has initiated a Phase 2 trial evaluating ABP-745 for the treatment of acute gout flares, comparing it to both placebo and colchicine.
“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,” stated William Dongfang Shi, PhD, Founder and CEO of Atom, in a company release. “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.”
These findings suggest that lingdolinurad and its companion compound, ABP-745, represent promising new therapeutic options for individuals grappling with the challenges of gout and hyperuricemia.
