Eloxx Pharmaceuticals has received clearance from the US Food and Drug Administration for its investigational new drug application for exaluren in nonsense mutation autosomal dominant polycystic kidney disease, known as ADPKD. The company announced the clearance on 29 October 2026. The decision allows Eloxx to open United States sites for EXPRESS, its Phase 2 study, and the company is activating sites in the United States and other countries ahead of first patient dosing in the third quarter of 2027.
ADPKD is the most common inherited kidney disease, affecting an estimated 160,000 to 200,000 people in the United States, according to Eloxx. It is caused by mutations in PKD1 or PKD2, genes encoding polycystin-1 and polycystin-2. An estimated 26 percent of those 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 decline in kidney function. ADPKD is a leading genetic cause of kidney failure.
Exaluren is designed to address the genetic cause in this subgroup. Eloxx describes the drug as a small molecule ribosomal modulator that promotes readthrough of premature stop codons caused by nonsense mutations, enabling production of full length, functional protein. Peer reviewed preclinical data show it restores full length polycystin-1 in cells carrying PKD1 nonsense mutations and partly corrects disease linked signalling pathways, according to the company October update. No human efficacy result in ADPKD has been reported yet, and the Phase 2 trial will test whether that laboratory effect translates into slower kidney growth in patients.
How the exaluren EXPRESS trial is designed
EXPRESS will enrol about 60 adults with genetically confirmed PKD1 or PKD2 nonsense mutations, randomised one to one to exaluren or placebo for 52 weeks. The primary end point is the annualised rate of change in height adjusted total kidney volume, assessed by magnetic resonance imaging at baseline and at weeks 28, 36 and 52. Topline 52 week results are expected in the first half of 2029.
The trial design was finalised in October 2026 after discussions with regulators and clinical leaders, Eloxx said. The company also appointed T.R. Srinivas as senior vice president and chief medical officer, joining from Novartis. Sumit Aggarwal, president and chief executive officer of Eloxx, said: “IND clearance is an important milestone for people living with nonsense-mutation ADPKD, who have no therapy that addresses the genetic cause of their disease.” He added that with the trial design finalised, the focus now is execution, activating sites and preparing to dose the first patient in the third quarter of 2027.
Eloxx is a clinical stage company listed on Nasdaq under the ticker ELOX, and exaluren is its lead product candidate. Exaluren is being developed for nonsense mutation Alport syndrome, another rare kidney disease caused by nonsense mutations.
What FDA feedback says about exaluren approval
In written pre-IND feedback, the FDA noted that a substantial and durable height adjusted total kidney volume treatment effect, with supporting kidney function and safety data, could serve as a possible basis for Breakthrough Therapy Designation. The FDA also identifies change in height adjusted total kidney volume as a possible surrogate end point for accelerated approval in ADPKD. Any expedited pathway would depend on clinical results and further FDA discussions.
Exaluren holds orphan drug designation for ADPKD in the United States and Europe, and for Alport syndrome. Orphan drug designation is intended to encourage development of treatments for rare diseases, and it does not by itself show that a drug works. The trial will need to show a kidney volume effect, supported by kidney function and safety data, before regulators consider those faster routes.
For patients with nonsense mutation ADPKD, the immediate change is limited. Site activation is under way, dosing is planned for the third quarter of 2027, and topline results are not expected until the first half of 2029. The clearance lets the trial open in the United States, but evidence on whether exaluren helps patients will come only from the trial itself.
Why exaluren research focuses on nonsense mutations
Nonsense mutations create a premature stop signal in a gene, so the cell stops building the protein too early and the resulting protein is incomplete. In ADPKD, that loss of functional polycystin is linked to cyst formation and kidney enlargement. A readthrough approach aims to let the ribosome pass that stop signal and produce a full length protein. That idea is why the trial enrols only patients with genetically confirmed nonsense mutations, rather than all patients with ADPKD.
The narrow enrolment also shapes how the results should be read. About 60 patients, split between the drug and placebo, is a small trial, and a kidney volume result in that group would still need confirmation in larger studies before any claim about long term kidney failure could be made.