Lingdolinurad (ABP-671) for Chronic Kidney Disease with Hyperuricemia
Hyperuricemia and chronic gout are widely recognized as independent risk factors for chronic kidney disease (CKD). ABP-671, which is in global Phase 3 trials for treatment of chronic gout and hyperuricemia, also has shown promise for hyperuricemia patients with CKD and a Phase 2 clinical trial is underway.
ABP-671 is a next-generation, highly selective oral urate transporter 1 (URAT1) inhibitor designed to lower the excessive serum uric acid (sUA) levels that lead to hyperuricemia, the cause of chronic gout. Impaired renal function reduces urate excretion and contributes to hyperuricemia, while urate crystal deposition in the kidneys and chronic inflammation may further worsen renal injury [1]. Consequently, effective long-term management of gout and hyperuricemia requires therapies capable of maintaining sustained sUA reduction while remaining safe for patients with renal impairment.
In preclinical studies, ABP-671 not only demonstrated urate-lowering efficacy but also effectively reduced renal interstitial fibrosis and renal urate crystal deposition, while showing potential to alleviate tubular necrosis and inflammatory cell infiltration, all of which are linked to the development and progression of CKD.
The Phase 2 clinical trial in CKD was launched following positive results from a clinical trial of ABP-671 in subjects with different levels of renal function. The results showed that a single oral 2.0 mg dose of ABP-671 was well tolerated in subjects with normal renal function and in patients with mild or moderate CKD.
With a favorable safety profile and significant urate-lowering efficacy at a low dose, ABP-671 has the potential to become a safer and more effective new treatment option for patients with CKD accompanied by hyperuricemia.
Market Opportunity and Limitations of Existing Therapies
CKD with hyperuricemia has become an increasingly serious global health concern. According to Frost & Sullivan, the global patient population increased from 388.5 million in 2021 to 435.3 million in 2025. The global population of patients with CKD and hyperuricemia is expected to reach 502.4 million by 2030.
The global market for therapies for CKD with hyperuricemia was approximately $1 billion in 2021 and is expected to reach $3.1 billion by 2030.
Currently, the major classes of marketed and investigational therapies for CKD with hyperuricemia include xanthine oxidase (XO) inhibitors and URAT1 inhibitors. Conventional XO inhibitors, such as allopurinol and febuxostat, are primarily used as monotherapies and provide only modest benefits in slowing the decline in estimated glomerular filtration rate (eGFR), an indicator of how well kidneys filter wastes from blood. These treatments also present important safety concerns, including the risks of severe hypersensitivity reactions and liver function abnormalities.
Other URAT1 inhibitors, such as probenecid and benzbromarone, may also be used to treat CKD with hyperuricemia. However, their use requires regular patient monitoring due to risks including renal complications and hepatotoxicity.
References
- Stamp LK, Farquhar H, Pisaniello HL, et al. Management of gout in chronic kidney disease: a G-CAN Consensus Statement on the research priorities. Nat Rev Rheumatol. 2021 Oct;17(10):633-641.