FDA Roundup: Pipeline Drugs for Gout

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Gout, an inflammatory form of arthritis characterized by the buildup of uric acid crystals in the joints, presents a significant health challenge due to its painful and debilitating effects.1 In recent years, there have been promising advancements in gout treatment, particularly with innovative developments entering phase 3 clinical trials. These emerging interventions not only target the acute symptoms of gout but also aim to address the underlying cause — hyperuricemia — with the goal of achieving lasting reductions in serum urate levels.1 From advanced xanthine oxidase inhibitors to groundbreaking strategies in specific NOD-like receptor family, pyrin domain-containing 3 protein (NLRP3) inflammasome modulation, these emerging therapies have the potential to reshape the landscape of gout management.

The emergence of “me-too” drugs, which are compounds that bear structural resemblance to existing medications, have become common in gout treatment.2 While these drugs often provide alternative options for patients, there is a growing recognition of the necessity for truly innovative treatments in the realm of gout care. Me-too drugs may offer incremental improvements in efficacy or safety profiles, but they do not always address the fundamental challenges associated with gout, such as hyperuricemia and crystal deposition.2

Novel gout treatments are specifically designed to target unique pathways, presenting the potential for more substantial advancements in managing the disease. Developing therapies that not only alleviate symptoms but also modify the underlying disease process is crucial for enhancing long-term outcomes and preventing disease progression. Striking a balance between refining existing treatment options and pioneering innovative approaches is essential for meeting the diverse needs of individuals with gout and for fostering a comprehensive and effective therapeutic arsenal for this prevalent condition.

The expanding armamentarium for gout treatment has seen notable additions in the form of novel therapeutic drug classes, offering enhanced precision in targeting the underlying mechanisms of hyperuricemia such as:

Urate Transporter-1 (URAT-1) Inhibitors

The renal transport protein URAT-1 plays a crucial role in reabsorbing uric acid in the kidneys, leading to elevated serum urate levels. The mechanism of URAT-1 inhibitors involves selectively blocking this transporter’s activity, hindering uric acid reabsorption and promoting its excretion. By disrupting this key step in uric acid handling, these inhibitors effectively reduce circulating urate levels. This not only addresses acute gout symptoms but also targets the root cause of hyperuricemia. The selectivity of URAT-1 inhibitors in modulating uric acid reabsorption sets them apart from conventional therapies, making them a promising and targeted approach for individuals who do not respond optimally to existing treatments.3,4


Epaminurad, also known as URC102/UR-1102, is currently in the phase 3 recruiting stage (ClinicalTrials.gov Identifier: NCT05815901), where it is being investigated in a randomized controlled trial (RCT) comparing its efficacy and safety with febuxostat for the treatment of patients with gout. Favorable safety, pharmacokinetics, and pharmacodynamics data were obtained from 3 phase 2 trials (ClinicalTrials.gov Identifiers: NCT02290210, NCT02557126, NCT04804111). The trials revealed a well-tolerated safety profile, highlighting promising outcomes in terms of safety, drug processing, and interactions within the body.5


SHR4640 is currently in the phase 3 recruiting stage (ClinicalTrials.gov Identifier: NCT04956432), where it is being investigated in an RCT for primary gout maintenance, comparing its efficacy and safety with allopurinol.


AR882 is being prepared to enter into a phase 3 clinical trial for clinical stage development after favorable outcomes from a phase 2b study (ClinicalTrials.gov Identifier: NCT05119686). Results of the phase 2b study demonstrated that AR882, when administered for 6 months, safely and effectively reduced serum uric acid levels, resolved tophus, and dissolved total crystal volume in patients with gout.6


ABP-671 is currently in the phase 2b/3 recruiting stage (ClinicalTrials.gov Identifier: NCT05818085) where it is being investigated in an RCT to assess its efficacy and safety for primary gout maintenance. The first part of the study will compare various doses and regimens against a placebo and allopurinol, while the second part will assess the selected dosing regimen(s) against a placebo in participants not initially enrolled in part 1.


SAP-001 is currently in the phase 2b recruiting stage (ClinicalTrials.gov Identifier: NCT05690204), where it is being investigated in an RCT to validate the safety, efficacy, and pharmacological characteristics of the following orally administered doses: 10 mg daily, 30 mg daily, and 60 mg daily, when compared with a placebo. SAP-001 demonstrated favorable results with significant reductions in serum uric acid levels compared with a placebo in previous phase 1/2 studies (ClinicalTrials.gov Identifier: NCT03857165). It was tolerated at daily doses of 120 mg or less in a single administration and 60 mg daily for 28 days.


D-0120 is currently in the phase 2b recruiting stage (ClinicalTrials.gov Identifier: NCT05504083), where it is being investigated in an RCT to assess its efficacy and safety for primary gout maintenance.

As these novel inhibitors progress through clinical trials, their mechanism of action holds the potential to offer enhanced efficacy and improved outcomes, marking a significant stride in the pursuit of more tailored and effective gout management.

Xanthine Oxidase Inhibitors

Xanthine oxidase is the enzyme responsible for converting purines into uric acid. Inhibiting this enzyme is a crucial strategy for reducing urate synthesis. Unlike traditional xanthine oxidase inhibitors, newer agents demonstrate enhanced specificity and potency, effectively reducing uric acid production while minimizing unintended effects. By blocking this enzymatic step, these inhibitors help prevent the accumulation of uric acid crystals in joints, a characteristic feature of gout. The efficacy of novel xanthine oxidase inhibitors extends beyond alleviating acute gout symptoms to addressing the chronic nature of hyperuricemia. This targeted approach not only aims to provide relief during gout flares but also seeks to normalize and maintain serum urate levels in the long term.7


Tigulixostat, also known as LC350189, is currently in the phase 3 recruiting stage for 2 RCTs. EURELIA1 (ClinicalTrials.gov Identifier: NCT05586958) is a 6-month study assessing the safety and efficacy of the following administered doses: 100 mg daily, 200 mg daily, and 300 mg daily, compared with a placebo. EURELIA2 (ClinicalTrials.gov Identifier: NCT05586971) is a 12-month study assessing the safety and efficacy of the following administered doses: 100 mg daily, 200 mg daily, and 300 mg daily, compared with allopurinol. In previous phase 2 studies, tigulixostat demonstrated significant reductions in serum urate and a tolerable safety profile when compared with a  placebo.8

Ongoing clinical trials, including EURELIA1 and EURELIA2, are poised to provide valuable insights into the safety and effectiveness of Tigulixostat, potentially leading to significant advancements in the field of gout therapeutics.


The innovative combination of pegylated recombinant uricase (pegadricase) and immune tolerance technology for mammalian target of rapamycin (mTOR; ImmTOR™) inhibitors represents a significant breakthrough in redefining gout treatment. This approach addresses both the symptoms and underlying causes of hyperuricemia. Pegadricase acts as a powerful enzyme that converts uric acid into a soluble compound, facilitating efficient elimination from the body. The addition of polyethylene glycol enhances the stability of uricase and prolongs its activity, resulting in the sustained and effective reduction of serum urate levels.9

In parallel, ImmTOR™ inhibitors reduce the development of antidrug antibodies and modulate the immune response, reducing the likelihood of immunogenic reactions against the therapeutic enzyme and extending its half-life.9,10

This combination therapy not only provides immediate relief from gout flares but also aims to offer a more long-lasting and targeted solution by addressing the chronic nature of hyperuricemia. By promoting uric acid breakdown and minimizing immune responses simultaneously, the synergy between pegylated uricase and ImmTOR™ inhibitors offers a comprehensive approach to gout management. It showcases the potential for transformative outcomes in patients who may have encountered limitations with traditional treatments.9,10


Pegadricase, also known as SEL-212 and previously referred to as pegsiticase during developmental stages, completed 2 phase 3 studies: DISSOLVE I (ClinicalTrials.gov Identifier: NCT04513366) and DISSOLVE II (ClinicalTrials.gov Identifier: NCT04596540). In the phase 3 trials, both SEL-212 doses (ImmTOR™ 0.1 mg/kg and 0.15 mg/kg, and a single dose of 0.2 mg/kg of pegadricase) exhibited significant response rates. Specifically, the high-dose group demonstrated response rates of 56% in DISSOLVE I and 46% in DISSOLVE II. These outcomes effectively fulfilled primary efficacy endpoints by sustaining serum urate levels below 6 mg/dL for at least 80% of the sixth 28-day treatment period, showcasing substantial reductions compared with a placebo.11

As clinical trials progress, the combination of pegylated uricase and ImmTOR™ inhibitors holds potential for reshaping the landscape of gout management, offering a potential breakthrough for individuals with refractory or advanced forms of the disease.

NLRP3 Inhibitors

The discovery of new inhibitors for the NLRP3 inflammasome has generated considerable interest for advancing the treatment options for gout. The NLRP3 inflammasome plays a crucial role in the inflammatory process, leading to the release of interleukin-1 beta, a cytokine associated with gout flares. These inhibitors specifically target the activation of the NLRP3 inflammasome, aiming to reduce the inflammatory response linked to crystal-induced gouty arthritis. By precisely modulating the innate immune system, these innovative agents have the potential to offer a more targeted and effective approach to managing acute gout attacks.12,13


Dapansutrile, also known as OLT1177, is currently in the phase 2/3 recruiting stage (ClinicalTrials.gov Identifier: NCT05658575), where its efficacy and safety are being investigated for the treatment of patients with acute gout flares. Results from the phase 2a proof-of-concept study demonstrated that treatment was well-tolerated with a favorable safety profile and was effective for decreasing joint pain.13

As clinical trials assessing the safety and efficacy of NLRP3 inflammasome inhibitors progress, there is growing optimism that these therapies may represent a significant breakthrough in providing relief for individuals with gout by directly addressing the underlying inflammatory pathways involved in its development.

The integration of URAT-1 inhibitors, newer xanthine oxidase inhibitors, uricolytics, and NLRP3 inhibitors into the therapeutic landscape reflects the ongoing commitment to refining gout treatment. As these innovative agents progress through clinical trials and gain regulatory approval, they hold the promise of providing more personalized and effective solutions for individuals with gout.

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