Eloxx的exaluren获FDA新药临床试验许可：将启动无义突变多囊肾病全球2期研究，约60名患者入组
总部位于 Massachusetts 州 Arlington 的临床阶段生物制药公司 Eloxx Pharmaceuticals 10月29日宣布，美国食品药品监督管理局（FDA）已批准其候选药 exaluren 的新药临床试验（IND）申请，用于治疗无义突变型常染色体显性多囊肾病（ADPKD）。公司可据此在美国启动其全球2期研究 EXPRESS 的临床中心。
ADPKD 是最常见的遗传性肾病，美国患者估计有16万至20万人。致病基因 PKD1 与 PKD2 的突变中，约26%为无义突变；功能性多囊蛋白缺失会导致肾脏囊肿不断形成与增大、肾体积增加、肾功能持续下降，该病是肾衰竭的主要遗传性病因。
EXPRESS 研究计划入组约60名经基因确认携带 PKD1 或 PKD2 无义突变的成人，按1比1随机分配至 exaluren 组或安慰剂组，治疗52周。主要终点是经身高校正的总肾体积（htTKV）年化增长率，以磁共振成像在基线及第28、36、52周评估。首例患者给药预计在2027年第三季度，52周顶线数据预计在2029年上半年。
监管路径方面，FDA 在 IND 前书面反馈中表示，若 htTKV 出现显著且持久的改善、并有肾小球滤过率与安全性数据支持，可能构成突破性疗法认定的基础；FDA 也把 htTKV 变化列为加速批准的潜在替代终点。exaluren 已在美国与欧洲获得 ADPKD 孤儿药资格。
exaluren 是一种小分子核糖体调节剂，设计上促进无义突变造成的提前终止密码子的通读，使细胞能生成全长、有功能的蛋白。公司首席执行官 Sumit Aggarwal 表示，IND 获批对尚无针对遗传病因疗法的无义突变 ADPKD 患者是重要里程碑，公司接下来将专注于启动中心并为2027年第三季度首例给药做准备。
Eloxx Wins FDA IND Clearance for Exaluren in Nonsense-Mutation Polycystic Kidney Disease, Clearing a Global Phase 2 Trial of About 60 Patients
Eloxx Pharmaceuticals, a clinical-stage biopharmaceutical company based in Arlington, Massachusetts, announced on October 29 that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for exaluren in nonsense-mutation autosomal dominant polycystic kidney disease (ADPKD), enabling the company to open U.S. sites for EXPRESS, its global Phase 2 study.
ADPKD is the most common inherited kidney disease, affecting an estimated 160,000 to 200,000 people in the United States. An estimated 26% of PKD1 and PKD2 mutations are nonsense mutations. Loss of functional polycystin leads to progressive formation and enlargement of fluid-filled kidney cysts, increasing kidney volume and causing a steady decline in kidney function; ADPKD is a leading genetic cause of kidney failure.
EXPRESS is designed to enroll approximately 60 adults with genetically confirmed PKD1 or PKD2 nonsense mutations, randomized 1:1 to exaluren or placebo for 52 weeks. The primary endpoint is the annualized rate of change in height-adjusted total kidney volume (htTKV), assessed by MRI at baseline and Weeks 28, 36 and 52. First patient dosing is expected in the third quarter of 2027, with topline 52-week data expected in the first half of 2029.
In written pre-IND feedback, the FDA noted that a substantial and durable htTKV effect, with supporting eGFR and safety data, could support Breakthrough Therapy Designation, and the agency lists htTKV change as a potential surrogate endpoint for accelerated approval in ADPKD. Exaluren holds orphan drug designation for ADPKD in the United States and Europe.
Exaluren is a small-molecule ribosomal modulator designed to promote readthrough of premature stop codons caused by nonsense mutations, enabling production of full-length, functional protein. President and CEO Sumit Aggarwal said IND clearance is an important milestone for people with nonsense-mutation ADPKD, who have no therapy addressing the genetic cause of their disease, and that the company will now focus on activating sites ahead of first dosing in the third quarter of 2027.
来源：GSM·美国（原文链接）
图片来源：图：腹部 CT 影像检查实景（资料图，与多囊肾病影像评估题材相关）。Goleisureintl 摄，CC BY 4.0，经 Wikimedia Commons。Photo: An abdominal CT imaging scan (file photo). Goleisureintl, CC BY 4.0, via Wikimedia Commons.
