Tigulixostat

伊顿健康导读 痛风，被称为“疼痛之王”的代谢性疾病，正迎来治疗变革。《2021年中国高尿酸及痛风趋势白皮书》显示，我国高尿酸血症患者约1.77亿，痛风已成仅次于糖尿病的第二大代谢类疾病。 传统治疗手段存在局限，急性期药物如非甾体抗炎药可能致肾损害，苯溴马隆有肝毒性隐患。未满足的临床需求推动新一代痛风治疗药物研发。 2025年11月，由中华预防医学会风湿病预防专业委员会牵头，邹和建等教授领衔，多学科专家制定的《痛风抗炎症治疗指南（2025版）》发布。这是全球首部痛风抗炎症治疗权威指南，标志我国痛风诊疗从“降尿酸为主”进入“抗炎与降尿酸并重”新时代。 一、为什么痛风治疗必须“抗炎+降尿酸”双管齐下？ 长期以来，痛风治疗重降尿酸、轻炎症控制，致患者复发、关节及器官受损。临床显示，仅降尿酸治疗，患者依从性不足50%，40%仍频繁发作，未联合抗炎治疗的患者痛风石形成率达22%，5年内复发超60%。 这些数据表明，单纯降尿酸难控痛风，新指南强调抗炎与降尿酸达标并重，实现“双达标”才能改善预后。 二、指南核心解读：痛风四大关键场景，精准抗炎全覆盖 场景一：急性发作期——尽早干预，严重者可考虑IL - 1抑制剂 指南明确，痛风急性发作需在36小时内（优先12小时内）抗炎。 一般患者：一线选低剂量秋水仙碱或达峰时间短的NSAIDs，也可用糖皮质激素。 严重发作患者：可联用2种不同类抗炎药，联用不佳推荐IL - 1抑制剂单用或联合用药。 特殊人群：对一线药不耐受等情况，推荐IL - 1抑制剂。 二、指南核心解读：四大关键场景，精准抗炎全覆盖 场景一：急性发作期——尽早干预，严重者可考虑IL - 1抑制剂 指南明确，痛风急性发作需在36小时内（优先12小时内）抗炎。 一般患者：一线选低剂量秋水仙碱或达峰时间短的NSAIDs，也可用糖皮质激素。 严重发作患者：可联用2种不同类抗炎药，联用不佳推荐IL - 1抑制剂单用或联合用药。 特殊人群：对一线药不耐受等情况，推荐IL - 1抑制剂。 场景二：合并基础病患者——个体化用药，生物制剂提供新选择 合并心血管疾病：建议用秋水仙碱或IL - 1抑制剂，可考虑糖皮质激素，谨慎用NSAIDs。 合并消化系统疾病： 合并腹泻等：建议IL - 1抑制剂或外用NSAIDs，单关节受累可关节腔注射糖皮质激素。 合并溃疡者：积极治合并症，可考虑秋水仙碱等，不推荐糖皮质激素或NSAIDs全身用药。 合并肝功能损害者：首选糖皮质激素等，用秋水仙碱等应减量并监测。 合并慢性肾脏病： G1 - G2期：建议秋水仙碱等，可考虑NSAIDs。 G3期：建议糖皮质激素等，可考虑减量秋水仙碱。 G4 - G5期：建议糖皮质激素，可考虑IL - 1抑制剂，禁用NSAIDs，G4期酌情减量秋水仙碱，G5期禁用。 场景三：痛风石患者——长程抗炎，保护关节与脏器 痛风石患者易受损，指南建议用秋水仙碱或IL - 1抑制剂长疗程抗炎，降低风险。 场景四：起始降尿酸治疗——预防性抗炎，减少发作 指南推荐用0.5mg/天秋水仙碱预防，严重者可增至1mg/天，不耐受建议IL - 1抑制剂等，仍不适用可考虑NSAIDs。 三、痛风创新药物密集上市，治疗格局被重新定义 2024年12月，新型URAT1抑制剂多替诺雷在中国率先上市；2025年初，恒瑞医药SHR4640申报上市获受理；6月，三生国健提交抗IL - 1β单抗上市申请，一品红公布氘泊替诺雷（AR882）积极临床数据；7月，金赛药业伏欣奇拜单抗获批用于急性痛风性关节炎。不到一年，多个药物密集申报或上市。 业内认为，“精准降酸”“靶向抗炎”新时代开启，诸多新药在多靶点形成梯队，全球痛风治疗格局或被重新定义。 四、痛风主流技术路径一：尿酸代谢通路精准调控 1. XO抑制剂——从别嘌呤醇到新一代非嘌呤类药物 1966年别嘌呤醇获FDA批准后，黄嘌呤氧化酶（XO）抑制剂成降尿酸重要策略。因嘌呤类药物副作用大，非嘌呤类XO抑制剂取得进展，如2009年美国上市的非布司他和2013年日本获批的托吡司他，疗效优于别嘌呤醇，但也有副作用，托吡司他仅在亚洲国家上市。 LG化学研发的Tigulixostat进展较快，已进入III期临床，适用于不耐受传统XO抑制剂的痛风患者。2022年12月，信达生物引进其中国权益（IBI350）。II期研究显示，其疗效显著优于安慰剂和非布司他。 2. URAT1抑制剂——痛风新一代高选择性药物 尿酸盐转运蛋白1（URAT1）是促尿酸排泄关键靶点，上市的主要有苯溴马隆和多替诺雷。 苯溴马隆因严重肝毒性在欧美撤市，仅在亚洲国家受限使用。日本卫材的多替诺雷2024年12月在中国获批上市，规避了肝毒性风险。中国III期数据显示，其疗效显著优于非布司他。 URAT1靶点是热门研发方向，超10款药物处于临床不同阶段。恒瑞医药的SHR4640是国内进度最快的URAT1抑制剂，2025年1月上市申请获受理。II期数据显示，其联合治疗效果显著优于安慰剂联合组。 一品红的氘泊替诺雷2024年获美国FDA快速通道资格，2025年3月完成全球III期入组。IIb试验数据亮眼，且安全性良好。 此外，有企业开发XO/URAT1双靶点抑制剂，可双重降尿酸。辉瑞的PF - 06743649因肾损伤终止研发，国内代表项目有通化东宝的THDBH151片（II期临床）和东阳光药的HEC93077。 3. 尿酸氧化酶类药物——难治性痛风的新选择 尿酸氧化酶类药物催化尿酸转化为尿囊素，为痛风治疗提供新思路。已上市的拉布立酶和普瑞凯希，因免疫原性强、价格贵且易耐药，应用受限。当前研发重点是降低免疫原性，如聚乙二醇化修饰或联合免疫调节剂。 进展较快的SEL - 212已提交上市申请，结合聚乙二醇化尿酸酶与ImmTOR免疫调节技术，可减少抗药物抗体形成、延长疗效。III期研究显示，高剂量组治疗6个月后缓解率分别达56%和47%。该药每月给药一次，提升患者依从性，有望成新治疗选择。 五、痛风主流技术路径二：炎症信号通路靶向阻断 痛风急性发病核心机制是尿酸盐晶体被吞噬后诱导NLRP3炎性体形成，激活半胱天冬酶，引发炎症反应释放细胞因子，最终导致痛风症状。抑制该炎症途径任一环节的药物，对痛风治疗有帮助。 1. IL - 1抑制剂——改写痛风抗炎治疗逻辑 全球已批准多个IL - 1抑制剂，阿纳白滞素、利纳西普未获批痛风适应症。2023年8月，卡那奴单抗成FDA首个急性痛风性关节炎IL - 1β抑制剂。 2025年7月，金赛药业伏欣奇拜单抗国内获批，适用于特定成人痛风性关节炎急性发作患者。III期数据显示，其72小时疼痛VAS评分改善非劣于复方倍他米松，24周时首次复发风险降低87%，安全性优于激素组。 除伏欣奇拜单抗，三生国健IL - 1β单抗SSGJ - 613针对痛风性关节炎适应证已递交上市申请，交晨生物GR007处于临床Ⅱ期。SSGJ - 613 III期研究显示，在疼痛缓解和预防复发方面达双主要疗效终点，预防复发显著优于阳性对照药。 2. NLRP3炎症小体抑制剂——从源头阻断炎症启动 NLRP3炎性小体是痛风炎症“上游开关”，抑制它可从源头阻断炎症，是研发热点。全球尚无上市品种，进展最快的Dapansutrile处于临床II/III期。 二、新兴前沿技术：siRNA药物实现“一针长效” 2025年6月，丽珠集团YJH - 012注射液临床试验申请获NMPA批准。 该药物通过GalNAc肝靶向递送系统将siRNA递送至肝脏，在肝细胞内切割靶蛋白mRNA，阻断尿酸生成通路。依托多种优势，YJH - 012单次给药可3 - 6个月持续降尿酸，临床前研究初步验证安全性。 区别于传统药物，YJH - 012采用siRNA技术，有望从基因层面长效抑制尿酸生成，若临床成功，将改变痛风治疗模式。 临床招募 目前有类似靶点的临床项目在开展，符合条件、用药、体检由申办方承担，不收取费用，同时会有交通补贴和营养补贴。 有需要的患者可以【扫描下方二维码报名登记】 也可添加客服二维码详细咨询 参考文献： 1. 中华预防医学会风湿病预防专业委员会. 痛风抗炎症治疗指南(2025版) ［J ］. 中华风湿病学杂志, ，2025, 29(11）：897-922.DOI:10.3760/cma.j.cn141217-20250926-00286 2. 中华预防医学会风湿病预防专业委员会,朱小霞,段利华,等.痛风抗炎症治疗指南（2025版）[J].中国预防医学杂志,2025，26（11）：1302-1328.DOI：10.16506/j.1009-6639.2025.11.004. 本文仅做参考，不构成对任何药物或诊疗方案的推荐、推广或宣传，也不可替代专业医疗建议。如有问题，请咨询医疗卫生专业人士。材料图片等源自网络，侵删。

SAN FRANCISCO and SUZHOU, China, Dec. 9, 2025 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major disease areas, announced that the first participant has been successfully dosed in a Phase 1 clinical trial of IBI3011, an anti-human Interleukin 1 receptor accessory protein (IL-1RAP) monoclonal antibody developed by Innovent. This study is a single ascending dose (SAD) study to evaluate the safety, tolerability, and pharmacokinetics of IBI3011 for the first-in-human administration, so as to support the subsequent clinical development of IBI3011. A total of 40 healthy volunteers and 24 patients with gout flares are planned to be enrolled. With economic development and rising living standards, the number of gout patients in China is increasing. By 2019, the estimated number of patients had exceeded 3 million.[1],[2] When serum uric acid rises above its saturation point, urate crystals can deposit in joints, triggering local inflammation and tissue damage and causing gout flares.[3] Recurrent flares can lead to joint destruction and functional impairment, limiting patients' social roles and seriously reducing quality of life. At present, first-line pharmacologic treatments for gout flare mainly consist of nonsteroidal anti-inflammatory drugs and colchicine, to which certain patients have contraindications or cannot tolerate, lacking targeted therapies. Second-line therapies as glucocorticoids are also associated with numerous adverse effects. In addition, only one IL‑1β–targeted agent has been approved in China for the treatment of gout flare, and there remains a large unmet need in clinical practice. IL-1RAP, a member of the IL-1 family, serves as a co-receptor that forms receptor complexes with IL-1R1, ST2, and IL-36R and mediates downstream signaling pathways triggered by IL1α/β, IL33 and IL36, respectively. These cytokines are implicated in a broad spectrum of autoimmune and inflammatory diseases including acute gouty arthritis, hidradenitis suppurativa, etc. Compared with anti‑IL‑1β antibodies, targeting IL‑1RAP can simultaneously block multiple IL‑1 family inflammatory pathways, with the potential to rapidly control inflammation, relieve gout symptoms, and enable earlier initiation of urate‑lowering therapy. IBI3011 is the first anti-IL ‑ 1RAP monoclonal antibody in China aimed to address inflammatory and autoimmune diseases. Preclinical data show that IBI3011 can significantly suppress gout flares in models of acute gouty arthritis, highlighting its clinical potential for the treatment of gout flares. In this therapeutic area, Innovent plans to initiate a Phase 3 trial of IBI128 (tigulixostat) in gout patients with hyperuricemia. Previously, the Phase 2 clinical results of IBI128 were presented at APLAR 2025 showing strong efficacy in reducing serum uric acid in patients with gout. On top of that, IBI3011 has the potential to further suppress gout flares, complementing tigulixostat's uric acid-lowering effect to provide a more comprehensive treatment approach for patients with hyperuricemia and gout. Additionally, Mazdutide could also provide the benefit of reducing blood uric acid in the obesity population. Together, these assets provide more personalized treatment options for patients with gout and hyperuricemia. With IBI3011 now entering the clinical stage, Innovent will further strengthen its pipeline in metabolic and autoimmune diseases. Dr. Lei Qian, Chief R&D Officer of General Biomedicine of Innovent Biologics, stated, "I am very pleased that the first participant has been dosed in the Phase 1 clinical study of IBI3011, and I look forward to its result supporting the development of treatments for gout flares and other indications. Innovent Biologics' general biomedicine pipeline reflects a well-structured, echeloned and matrix-like strategy across the fields of cardiovascular and metabolic diseases (CVM), autoimmune diseases, and ophthalmology. For gout, a metabolic and immune-related condition, IB3011 complements the promising Phase 2 clinical results of IBI128 (tigulixostat), which demonstrated excellent efficacy in targeting XOI and is now advancing to Phase 3. By focusing on next-generation global innovations, Innovent is accelerating the development of high-potential molecules and the synergy of these products is expected to bring more innovative therapies that improve the quality of life to patients around the world." About IBI3011 IBI3011 is a monoclonal antibody targeting IL‑1RAP. As a co‑receptor, IL‑1RAP forms receptor complex with IL‑1R1, ST2, and IL‑36R, hence mediating activation of the IL‑1α/β, IL‑33, and IL‑36α/β/γ signaling pathways and contributing to the development of multiple autoimmune and inflammatory diseases. Consequently, targeting IL‑1RAP can simultaneously block several IL‑1 family inflammatory pathways, with the potential to rapidly control inflammation, alleviate gout symptoms, and allow earlier initiation of urate‑lowering therapy. Preclinical data indicate that IBI3011 can significantly suppress gout flares in models of acute gouty arthritis, underscoring the clinical potential of IBI3011. About Innovent Biologics Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 17 products in the market. It has 1 new drug applications under regulatory review, 4 assets in Phase 3 or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Roche, Takeda, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action" Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: Innovent Biologics does not recommend the use of unapproved drugs/indications. Forward-Looking Statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Innovent Biologics