Atom Therapeutics Co., Ltd announced positive topline results from its global Phase 2b/3 clinical trial of lingdolinurad (ABP-671), a novel orally administered URAT1 inhibitor for chronic gout treatment. The multicenter, randomized, double-blind, six-month study successfully met its primary endpoint, demonstrating significant efficacy in lowering serum uric acid (sUA) levels while maintaining good safety and tolerability.
The study compared ABP-671 dose groups to allopurinol (Treat-to-Target) and placebo across four major global regions: United States, Europe, Latin America, and Australia. Statistical analysis indicated ABP-671 showed a therapeutic advantage over the positive control group receiving up to 800 mg/day of allopurinol under the Treat-to-Target dosing strategy to reach < 6 mg/dL of sUA.
Superior Uric Acid Control and Clinical Outcomes
ABP-671 demonstrated outstanding urate lowering effects, with a notably higher proportion of patients reaching more stringent sUA thresholds of < 5 mg/dL and < 4 mg/dL compared to the allopurinol group. The drug significantly reduced the relative risk of acute gout attacks with a maximum risk reduction of 42% within the period of 15-28 weeks compared to both allopurinol and placebo groups.
During the six-month treatment period, ABP-671 demonstrated remarkable efficacy in dissolving tophi with significant reduction in gouty stone compared to baseline levels. The response rate of tophus diameter reduction between baseline and week 28 reached 91%.
Safety Profile Addresses Current Treatment Limitations
ABP-671 demonstrated good safety and tolerability, with overall adverse events in the recommended Phase 3 clinical dose group comparable to those in the placebo group. Notably, compared to other urate lowering drugs such as febuxostat, benzbromarone and some investigational drugs that have shown cardiovascular risks and/or liver toxicity, ABP-671 has not shown any cardiovascular risks or liver toxicity.
Dr. William Dongfang Shi, Atom's CEO, Chairman and Founder, commented, "Robust clinical data have demonstrated the strong efficacy, safety, and tolerability of ABP-671, positioning it as a leading candidate for best-in-class therapeutic in this area."
Clinical Context and Unmet Medical Need
The American College of Rheumatology recommends lowering serum uric acid levels in gout patients to < 6 mg/dL to reduce gout flares and long-term joint damage. The British Society for Rheumatology and the European Alliance of Associations for Rheumatology further suggest controlling sUA to < 5 mg/dL to achieve functional remission in some patients.
However, an increasing number of clinical consensus guidelines support maintaining sUA levels at 4-5 mg/dL to optimize outcomes in gout management. Sustaining low uric acid levels allows continuous dissolution of tophus in joints and soft tissues, promoting reduction in both the size and number, thereby lowering the frequency of gout flares and ultimately achieving functional remission.
Currently available gout therapies demonstrate insufficient efficacy and are often associated with serious or even life-threatening adverse effects, such as severe hepatotoxicity, nephrotoxicity, higher risk of sudden death, heart disease, or gastrointestinal discomfort, falling far short of the ideal therapeutic needs.
Next Steps
Dr. Shi added, "The six-month global Phase 2b/3 clinical trial provided compelling evidence that ABP-671 is associated with clinically meaningful improvement in reducing the risk of acute gout attacks and promoting tophus dissolution. These findings lay the groundwork for the design and planning of our upcoming pivotal clinical studies."
Atom Therapeutics is a clinical stage biotechnology company focused on development of best-in-class small molecule therapeutics for treatment of inflammatory and metabolic diseases. The company's pipeline also includes ABP-745, another small molecule for anti-inflammatory and autoimmune conditions, which has completed Phase 1 clinical trials and demonstrated good pharmacokinetics and safety, with Phase 2 clinical studies currently ongoing.
