ABP-671: A New Hope for Gout Treatment? Safety, Tolerability, and Efficacy Explained (2026)

Picture this: millions of people suffering from the agonizing pain of gout, a condition triggered by skyrocketing uric acid levels in their blood, desperately seeking relief without the burden of severe side effects from today's medications. This groundbreaking research on ABP-671, a promising new drug, sheds light on a potential game-changer in gout treatment. But hold onto your seats—because as we dive into the science, you'll discover why this might not be as straightforward as it seems, and there's plenty of room for debate along the way.

Introduction

Gout stands out as a persistent inflammatory disease stemming from elevated serum uric acid (sUA) concentrations, often linked to disruptions in purine metabolism or the body's ability to excrete uric acid effectively. The prevalence of gout fluctuates widely, from under 1% to as high as 6.8%, depending on the populations examined and the methodologies employed, with an incidence rate between 0.58 and 2.89 cases per 1,000 individuals annually. When sUA levels aren't controlled adequately, chronic inflammation in the joints can ensue, potentially leading to the formation of tophi—those are hardened deposits of uric acid crystals encased in inflammatory tissue and scar tissue, which can irreversibly harm bones and cartilage. Alongside dietary changes and lifestyle adjustments, urate-lowering therapies (ULTs) play a key role in managing gout, aiming to keep sUA below 6 or even 5 mg/dL long-term.

ULTs encompass a range of options, including xanthine oxidase inhibitors like febuxostat and allopurinol, URAT1 inhibitors such as benzbromarone, probenecid, and lesinurad (the latter was pulled from global markets in 2019), as well as urate oxidase drugs like pegloticase. However, these treatments often fall short in terms of effectiveness and come with drawbacks, including severe liver and kidney damage, plus the added risk of cardiovascular issues with febuxostat. This has created an urgent need for novel, safer, and more potent ULT options.

Enter ABP-671, an innovative URAT1 inhibitor crafted by Atom Therapeutics Co., Ltd. This drug works by inhibiting uric acid reabsorption in the kidneys, specifically targeting the URAT1 protein found in the proximal tubules of the kidney's cortex—a process responsible for roughly 90% of uric acid reclamation. By blocking this, ABP-671 encourages more uric acid to be flushed out through urine, helping to lower sUA levels. Laboratory tests on Madin Darby canine kidney cells engineered to express human URAT1 showed that ABP-671 powerfully inhibits uric acid transport, with an IC50 value of 0.04 μM, far outperforming benzbromarone (0.14 μM) and lesinurad (24.36 μM). Animal studies in rats with hyperuricemia revealed quick absorption after oral dosing, along with notable drops in sUA and blood urea nitrogen at 15 and 25 mg/kg daily doses (data not yet published).

This comprehensive investigation explored ABP-671's safety, tolerability, pharmacokinetics (PK, which is how the body handles the drug), pharmacodynamics (PD, or the drug's effects on the body), and how food influences it, using single and repeated oral doses in both healthy volunteers and those with elevated uric acid levels.

Patients and Methods

Study Design

The research, carried out in the United States, comprised three distinct phases involving healthy participants and those with hyperuricemia. These included:

Single Ascending Dose (SAD) Study

This Phase I trial, conducted at a single site, was randomized, double-blind, and placebo-controlled, focusing on the safety, tolerability, PK, and PD of escalating single doses of ABP-671 in healthy adults. The dosages tested were 0.1, 0.5, and 1.0 mg, matched with two placebo groups and six participants per dose level. Everyone fasted for eight hours overnight before receiving a single oral dose of the drug or placebo, washed down with 240 mL of water.

Each dose group of eight people got ABP-671 (six) or placebo (two) in a blinded fashion. Within each group, two 'sentinel' subjects were chosen randomly—one for ABP-671 and one for placebo. Dosing for the full group only proceeded after these two showed no safety concerns in the 72 hours post-administration. Then, the remaining participants were assigned accordingly, with a minimum seven-day break before moving to the next dose level (see Figure 1A).

Multiple Ascending Dose (MAD) Study

This Phase Ib trial, randomized, double-blind, and placebo-controlled, assessed the safety, tolerability, PK, and PD of increasing daily oral doses of ABP-671 solution (taken once daily for 10 days) in hyperuricemic individuals who were otherwise in good health. The drug came as a 10 mL solution mixed with 3% sodium bicarbonate, followed by 480 mL of water, after an overnight fast from days 1 through 10.

Nine people per dose group (0.2, 0.5, and 1.0 mg/day) received ABP-671 (seven) or placebo (two), dosed once daily for 10 straight days in a fasted state, following the randomization plan. Progression to the next dose only happened after all nine in a group finished dosing and underwent 14 days of follow-up (Figure 1B). Any dropouts unrelated to treatment side effects were replaced.

Food-Effect Study

This single-center, open-label, single-dose, two-way crossover trial enrolled 12 healthy adults, randomized into two sequences (AB or BA). Sequence A involved a 1.0 mg tablet of ABP-671 on an empty stomach, while B meant taking it after a meal, each with about 240 mL of water. A four-day washout separated the two periods (Figure 1C).

Figure 1 illustrates the clinical trial setups. (A) Single ascending dose. (B) Multiple ascending dose. (C) Food-effect.

Ethical Considerations

All procedures adhered to the Declaration of Helsinki and the International Council for Harmonisation's Good Clinical Practice guidelines. Relevant documents were approved by Advarra Institutional Review Board (approval numbers MOD00398822 and MOD00507949) and IntegReview Institutional Review Board (various numbers). Participants gave written consent before any study activities. Trials are registered on clinicaltrials.gov: SAD (NCT03906006), MAD (NCT04303073), food-effect (NCT04303039).

Study Population

SAD Study

Inclusion: Ages 18-45; healthy by history, exams, ECG, and vitals; sUA 4.0-5.5 mg/dL (males) or 4.0-5.0 mg/dL (females); BMI 18.0-32.0 kg/m²; weight ≥50 kg.

Exclusion: Significant diseases, psychiatric issues, kidney stone history or suspicion, recent drug use (prescription, OTC, herbal, or HRT within 14 days), positive drug screens, major surgery in past 3 months, or other disqualifying conditions per investigator.

PK and PD Assessments

Blood (5 mL for PK, 2 mL for PD) and urine (for PD) were sampled at times in Supplementary Table S1. Drug levels measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parameters computed using non-compartmental methods in Phoenix® WinNonlin® Version 8.1.

Analysis of Food Effects

Variance analysis and linear models on log-transformed AUC0-t, AUC0-inf, Cmax compared fed vs. fasted states, with sequence, period, treatment fixed, subjects random. Geometric mean ratios (GMRs) and 90% CIs calculated; no effect if CI within 80-125%.

Safety Monitoring

Evaluated adverse events (AEs, SAEs), ECGs, vitals, exams, labs. Timed visits varied by study (detailed in text). AEs coded via MedDRA® v22.0, graded per DAIDS Table v2.1.

Statistical Analysis

Safety/PD sets: those receiving drug/placebo. PK sets: drug recipients. Placebo data pooled. Demographics: mean ± SD or n (%). PK/PD: geometric mean (CV%) or median (range). Safety: descriptive summary.

Results

Subjects Enrollment and Characteristics

SAD: 24 healthy participants—six per ABP-671 dose (0.1, 0.5, 1.0 mg), six placebo.

MAD: 27 hyperuricemic—seven per ABP-671 dose (0.2, 0.5, 1.0 mg/day), six placebo.

Food-effect: 12 healthy—six per sequence.

Ages averaged 30.7-47.1 years; BMIs 22.93-30.97 kg/m². Males dominated, 50-100% (Table 1).

Table 1: Participant Demographics.

Safety and Tolerability

TEAEs summarized in Supplementary Table S2. Incidences similar between groups.

SAD: 17% (0.1 mg), 17% (0.5 mg), 33% (1.0 mg), 13% (placebo)—all mild/moderate.

MAD: 29% (0.2 mg/day), 57% (0.5 mg/day), 14% (1.0 mg/day), 33% (placebo)—mostly grade 1.

PK

Plasma curves in Figure 2A-B (SAD) and 2C-D (MAD).

SAD: Median tmax 0.695-1.006 h; mean CL/F 3.436-3.651 L/h; t1/2 3.095-4.575 h. Cmax, AUCs, Vd/F rose with dose (Table 2).

MAD (Day 10): Median tmax,ss 1.000-1.003 h; CLss/F 5.042-5.992 L/h; t1/2 2.622-2.964 h. Cmax,ss, AUCtau dose-dependent (Table 2).

Dose proportionality for AUC0-t, AUC0-inf, Cmax in both studies (slope CI includes 1, Table 3).

Table 2: PK Metrics in SAD and MAD Day 10.

Table 3: Dose Proportionality.

PD

SAD: sUA dropped 3 hours post-dose, reductions escalating with dose. Max changes: 8.5% (0.1 mg), 29.9% (0.5 mg), 34.6% (1.0 mg) at 12-24 h. At 24 h: -6.8%, -23.8%, -26.5% vs. 2.1% placebo. Rebounded by 72 h (Table 4, Figure 3A).

MAD: Similar onset, dose-dependent drops. Max on Day 1: -12% (0.2 mg), -25% (0.5), -28% (1.0). 24 h reductions: Day 1 -5.5/-19.7/-20.6%; Day 5 -13.4/-24.1/-30.4%; Day 10 -11.7/-22.2/-26.6% vs. placebo -1.1/-4.4/-2.0%. Max Day 10: -23/-39/-44%. Returned near baseline by 72 h (Table 4, Figure 3B-D).

UA fractional excretion changes in Table 4 and Figure 4.

Table 4: PD Data in SAD/MAD.

Food Effect

AUC0-t, AUC0-inf, Cmax similar; GMR 90% CIs 80-125%. sUA, changes, excretion rates akin in fed/fasted states—no impact on PK/PD (Table 5, Figure 5).

Table 5: Food Impacts on PK/PD for 1.0 mg.

Figure 5: Food Effects on PK/PD Curves.

Discussion

This trio of studies (SAD, MAD, food-effect) evaluated ABP-671's safety, tolerability, PK, PD, and food interactions with single/repeated doses in healthy and hyperuricemic individuals. Findings show 0.1-1 mg doses over 10 days safe, well-tolerated, quickly absorbed. Exposure scales linearly with dose. sUA reductions quick, consistent, enduring. Food doesn't alter PK. This marks ABP-671's first human trials.

But here's where it gets controversial: URAT1 inhibitors are often cautioned against in kidney stone sufferers, due to risks like increased nephrolithiasis seen with benzbromarone. Studies on verinurad noted creatinine rises in 17.1% without stones, while URC102 had TEAEs in 41%. Our TEAEs were low (14-57% across doses, vs. 13-33% placebo), mild/moderate. Gastrointestinal issues, especially diarrhea (up to 17%), topped the list—but liver/cardiac events from other ULTs like dotinurad, benzbromarone, febuxostat weren't here. No SAEs, discontinuations, or fatalities, unlike some peers. This suggests ABP-671 might sidestep common pitfalls, but is it too good to be true? And this is the part most people miss: while short-term data looks promising, long-term risks could emerge, sparking debate on rushing new drugs to market.

PK mirrored other URAT1 inhibitors—dose-proportional Cmax/AUCs, consistent tmax/t1/2.

Effects kicked in fast (~3 h), peaking by 24 h, with PD tied to dose. 1.0 mg cut sUA 26% at 24 h (SAD), 20-30% over MAD days.

Controversially, food didn't hinder ABP-671, unlike verinurad's delayed absorption with meals. This flexibility could boost adherence, but does it mask potential interactions? We're inviting you to weigh in: Should drug manufacturers prioritize convenience over caution?

Limitations: Small groups, brief duration—may limit broad applicability and long-term insights.

Conclusion

Oral ABP-671 at 0.1-1 mg, single or multiple doses up to 10 days, proved safe, tolerable, fast-absorbing, with linear dose-exposure in humans. It markedly lowered sUA in hyperuricemics, with swift action. More trials needed to unlock its full promise for gout/hyperuricemia patients.

What are your thoughts? Do you believe ABP-671 could revolutionize gout treatment, or are you skeptical about its edge over existing options? Drop your opinions in the comments—we'd love to hear your take!

Data Sharing Statement

Datasets, including anonymized participant info, protocols, analyses, available on request with sponsor okay. Reviewed for validity; access up to 5 years post-publication. Contact corresponding author.

Acknowledgments

Thanks to all participants.

Author Contributions

Authors contributed to design, execution, analysis, writing.

Funding

None.

Disclosure

Authors: Atom Therapeutics Co., Ltd. employees.

References

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