Meeting unmet needs: new treatments for gout race in the clinic

Meeting unmet needs: new treatments for gout race in the clinic By Roohi Mariam Peter Add Labiotech as your Google Preferred Source 12 minutesmins July 29, 2026 12 minutesmins Share WhatsApp Twitter Linkedin Email Photo credits: Alicia Christin Gerald (Unsplash) Add Labiotech as your Google Preferred Source Newsletter Signup - Under Article / In Page"*" indicates required fieldsLinkedInThis field is for validation purposes and should be left unchanged.Subscribe to our newsletter to get the latest biotech news!By clicking this I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy.*Company name*Job title*Business email* Roughly half the people living with gout do not have treatments that work for them. While standards of care serve some of the population, many turn to calming gout flares with anti-inflammatory drugs that fail to address the root cause of the metabolic condition. Some biotechs are running clinical trials to reinstate a class of drugs that once faced commercial setbacks in the therapeutic field. One such biotech has just secured $130 million in funding to do so. Table of contentsTreating gout: why are current standards of care not enough? Gout is an inflammatory condition that is caused by the buildup of uric acid in the blood. Uric acid is the waste product from broken down purines, which are chemicals present in cells and certain foods. These high levels of uric acid, known as hyperuricemia, lead to the formation of uric acid crystals in the joints called tophi, prompting pain and swelling. There were more than 6 million new cases of gout recorded globally among people aged between 15 and 64 in 2021. According to a report by Mayo Clinic, people assigned male at birth are more likely to have high uric acid levels, increasing their risk of gout. The disease is typically treated in two ways. James Mackay, scientist and chief executive officer (CEO) of Crystalys Therapeutics, explained that the first approach is treating acute gout flares with non-steroidal anti-inflammatory drugs like colchicine as well as corticosteroids to reduce pain and inflammation. The second approach is to address the underlying cause of the disease, which is the accumulation of uric acid in the body. Long-term urate-lowering therapy reduced serum uric acid to a target level of under 6 mg/dL. The first-line standard of care urate-lowering therapy is allopurinol. It works by inhibiting the enzyme xanthine oxidase that blocks the conversion of certain molecules like hypoxanthine and xanthine into uric acid, lowering the chances of crystals from forming. Another xanthine oxidase inhibitor is febuxostat, but it is used less in the U.S. after the Food and Drug Administration (FDA) issued a boxed warning as it raised the risk of heart-related death in 2019. However, Mackay pointed out that both allopurinol and febuxostat are good at keeping uric acid buildup at bay only in around half the patient population, leaving 50% of patients stranded. “The remainder cannot tolerate them, have contraindications, or remain above their target serum uric acid level, despite treatment and dose escalation,” said Mackay. Moreover, the options beyond first-line care are limited. Probenecid removes uric acid from the body via the kidneys but cannot treat a sudden gout attack and needs to be taken several times a day. Mackay added that it is rarely used because of multiple drug-drug interactions. Meanwhile, intravenous uricase therapy is generally reserved for patients with severe, uncontrolled gout who have not responded to conventional oral treatments. “As a result, there remains a significant gap between first-line oral xanthine oxidase inhibitors and last-line uricase therapy. Patients who do not respond adequately to or cannot tolerate first-line therapy need an effective, convenient oral second-line option that can help them reach and maintain their serum uric acid target, reduce gout flares and resolve tophi,” said Mackay. New drug for gout: Crystalys Therapeutics’ URAT1 inhibitor in phase 3 studies Mackay’s Crystalys Therapeutics is developing a second-line therapy to bridge that gap and meet the needs of people living with gout. Dotinurad is a once-daily, oral, selective urate reabsorption inhibitor that targets urate transporter 1, known as URAT1. It is located in the proximal tubules of the kidneys and is responsible for reabsorbing uric acid from the urine back into the bloodstream. By inhibiting URAT1, dotinurad averts this reabsorption and allows uric acid to be rid of through the urine. Unlike xanthine oxidase inhibitors that lower uric acid levels by reducing their production, dotinurad addresses the kidney’s handling of uric acid by only hindering URAT1 and not any other transporters in the kidneys. Suggested Articles The biggest biotech funding rounds in September 2025 Eight of the biggest immunology and inflammation (I&I) deals in 2025 Targeting inflammation: A revolution in disease treatment Five recent advancements in arthritis research over the past year Six immunology biotech companies revolutionizing immune treatments in 2024 “We believe this differentiated mechanism, combined with dotinurad’s oral, once-daily administration, could provide an important second-line option for patients who do not respond adequately to or cannot tolerate existing first-line therapies,” said Mackay. Dotinurad is being investigated in phase 2 and 3 studies in the U.S. The phase 2 study is for people with gout who still have flare-ups but cannot take allopurinol or febuxostat as well as for whom uricase therapy did not work. The phase 3 study is for people with advanced and/or untreated gout, also known as tophaceous gout who are on allopurinol. People with this kind of gout develop tophi under the skin. The California-based company will push for regulatory approval in the U.S. and Europe, having been granted clearance in Japan in 2020 and China in 2024, where it is used as a first line treatment for people with asymptomatic hyperuricemia with or without gout. “The treatment approach is different from that used in U.S and the European Union,” said Mackay. “Dotinurad has performed well in a largely genericized market and has been taken by more than 2.2 million patients.” URAT1 inhibitors rush to hit endpoints To take it beyond the clinic, the company raised $130 million in a series B financing round a week ago, as it isn’t the only URAT1 inhibitor out there. Indeed, the URAT1 inhibitor pozdeutinurad is in phase 3 trials too. Formerly developed by Arthrosi Therapeutics, until it was acquired by the Stockholm-headquartered Swedish Orphan Biovitrum for $1.5 billion in February, pozdeutinurad garnered positive topline results from its ongoing phase 3 study in May. Patients were dosed with 75 mg and 50 mg of the therapy, and both doses met the primary endpoint. More than 69% of patients reached serum uric acid levels below 6 mg/dL and 56.5% of patients hit those levels on 50 mg after six months, compared to 8.1% of patients who took placebo. Further, the drug showed no unexpected safety signals. “We are very encouraged by these results and their implications for patients whose gout remains inadequately controlled,” said Lydia Abad-Franch, chief medical officer of Sobi, who added that the results point to “a strong foundation for regulatory submissions.” Pozdeutinurad’s encouraging performance so far softens the blow for Sobi after its own gout drug, nanoencapsulated sirolimus plus pegadricase (NASP), was rejected by the FDA last month. NASP is an intravenous infusion given to people living with uncontrolled gout every four weeks that breaks down uric acid in the body with the enzyme uricase while also employing the immunosuppressant nano-sirolimus, which is a part of the infusion, to block immune reactions against that enzyme. The therapy hit the primary endpoint when patients treated with NASP achieved and maintained serum uric acid levels below 6 mg/dL for at least 80% of the time after six months compared to placebo. The FDA’s thumbs down did not have anything to do with the efficacy results. It came with a request for additional data related to chemistry, manufacturing, and controls (CMC) and contract manufacturing facilities. Atom Therapeutics’ ABP-671 proves itself in clinic Another URAT1 inhibitor nearing the finish line is lingdolinurad, developed by Chinese company Atom Therapeutics. Lingdolinurad, dubbed ABP-671, is currently in phase 3 trials and the first person was dosed in June. This is following positive topline data released late last year. The study met all the primary and secondary endpoints after the candidate was tested against placebo and allopurinol. Patients who received the URAT1 inhibitor once daily in the doses 1 mg, 2 mg, 4 mg, 6 mg and 12 mg, experienced a reduction in serum uric acid levels, slashing the risk by 42% over 15 to 28 weeks. The candidate performed better compared to those who were on 800 mg/day of allopurinol. Lingdolinurad managed to bring serum uric acid levels down to 5 mg/dl and 4 mg/dl. It dissolved tophi over six months and about 91% of patients responded to the treatment after 28 weeks. The drug also showed “good safety and tolerability” as opposed to other urate lowering drugs linked to heart disease risks. These URAT1 inhibitors proving their safety and tolerability in late-stage trials is a big deal, considering older URAT1 inhibitors like benzbromarone have been linked to kidney toxicity and haven’t been approved by the U.S. Meanwhile, lesinurad, known by its brand name Zurampic, was greenlit by the FDA in 2015 for gout but it came with a boxed warning against liver failure. The drug performed poorly in the market which led to its eventual discontinuation in 2019. The class of drugs seem to be making a comeback, however, with the slew of positive data coming out of the clinic this year. Alternatives to allopurinol for gout: XORTX Therapeutics’ XRx-026 and more While the goal of these URAT1 inhibitors is to beat allopurinol’s efficacy, XORTX Therapeutics’ XRx-026, made from the subunit of allopurinol, is aimed at patients who are intolerant to allopurinol. The candidate contains oxypurinol, the active form of allopurinol that prevents xanthine oxidase from breaking down purines into uric acid. The Canadian company has tested XRx-026 in more than 750 people who cannot be on allopurinol, and it was found to have a better safety profile than allopurinol and febuxostat. While the company hasn’t published clinical data of the phase 3-candidate in recent times, it plans to file a new drug application (NDA) with the FDA, in hopes of bringing the drug to market this year. If approved, XORTX’s recent $5 million public offering could bolster the commercialization of XRx-026, which the company predicts will rake in $700 million every year. Meanwhile, Shanton Pharma and Protalix BioTherapeutics have been doing something different. Instead of blocking URAT1 like dotinurad and lingdolinurad, New Jersey-based Shanton’s SAP-001 targets another transporter called GLUT9. It halts the reabsorption of uric acid so that it can be expelled out of the body through urine. Topline results from a phase 2b trial were promising. Nearly all the patients who took 30 mg and 60 mg dosages of SAP-001 once every day on top of conventional therapy had serum uric acid levels reach below 6mg/dL, compared to about 10% of patients who were solely on conventional treatment. The company also stated that the study demonstrated an “excellent safety profile.” As for Protalix BioTherapeutics’ phase 1 candidate PRX-115, it is a PEGylated uricase enzyme. A PEGylated enzyme is one that has been modified to last longer in the body and lower the risk of an immune reaction. PRX-115 converts uric acid into allantoin, a harmless molecule that is easily removed through urine, reducing the risk of uric acid forming clumps. The candidate is being evaluated in phase 2 trials. Can Crystalys’ dotinurad close the gout treatment gap? As various candidates get ahead in the clinic, Crystalys’ dotinurad among the other URAT1 inhibitors are restoring confidence in this type of therapy to close the gap between commonly used oral urate-lowering medicines and intravenous treatments generally reserved for people with severe, uncontrolled gout. “If approved in the U.S. and Europe, dotinurad could provide people with gout an additional oral treatment option, particularly for those who cannot tolerate or do not respond adequately to current first-line therapies,” said Mackay. The $130 million series B funding will fuel commercialization efforts, if the FDA and the European Medicines Agency (EMA) sign off on the therapy. Mackay said: “Dotinurad’s differentiated mechanism is designed to help the kidneys eliminate more uric acid, potentially giving physicians another way to help patients reach and maintain their target serum uric acid levels. Ultimately, broader access to an effective, once-daily oral therapy could help more people manage the underlying cause of gout, reduce painful flares and prevent complications such as tophi and long-term joint damage.” This article is reserved for subscribers Subscribe for free to continue reading.Enter your details to log in or subscribe. Email Company name Job title Continue Readingor Continue with Microsoft Continue with LinkedIn By continuing, I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy. Immunology & inflammation R&D trends and breakthrough innovations Inpart’s new report provides scientific decision-makers with a roadmap of high-impact I&I opportunities, emerging technologies, and potential future partners. Download now Explore other topics: Clinical trialInflammatory diseaseMetabolic disordersSmall molecules ADVERTISEMENT