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.
Source: GSM · USA (original Chinese edition)
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