Eloxx Targets About 60 Patients in Kidney Study of Zorblisa, With Initial Results Expected in 2029
Key Facts
Eloxx Pharmaceuticals plans to test Zorblisa in a global Phase 2 study targeting about 60 adults with autosomal dominant polycystic kidney disease, limited to those with genetically confirmed nonsense mutations in the PKD1 or PKD2 genes. The company announced on October 20 that it had completed the design of the EXPRESS study, but did not say the U.S. Food and Drug Administration had granted IND authorization to begin it; its filing said enrollment in 2027 is conditional on completing the protocol and obtaining authorization. The company expects to dose the first participant in the third quarter of 2027, with initial results after 52 weeks due in the first half of 2029. This timeline puts the program years away from an initial efficacy readout. The drug targets a genetically defined subgroup of patients with ADPKD, not the broader population with the disease.
The study will randomly assign participants in a 1:1 ratio to Zorblisa or placebo, with treatment lasting 52 weeks. The primary endpoint is the annual rate of change in height-adjusted total kidney volume, known as htTKV. It will be measured by magnetic resonance imaging at baseline and at weeks 28, 36 and 52. The company’s chief executive said the year-long extension was designed to provide a more robust assessment of kidney-volume growth, while collecting kidney-function and safety data over a year. The design makes changes in kidney volume the primary focus of the assessment, with function and safety measures monitored during the same study period.
Eloxx said written feedback it received from the FDA before submitting its IND application indicated that a substantial and sustained effect on htTKV, supported by kidney-function and safety data, could form a potential basis for seeking breakthrough therapy designation. The agency also identifies changes in htTKV as a potential surrogate endpoint for accelerated approval in ADPKD. But this remains a potential regulatory pathway tied to the study’s results and subsequent discussions with the regulator. The FDA says drugs granted accelerated approval on the basis of a surrogate endpoint remain subject to studies confirming the expected clinical benefit. The study design and agency feedback therefore do not constitute approval of the drug or proof of its efficacy.
The company estimates that ADPKD affects about 160,000 to 200,000 people in the United States, and that about 26% of patients have nonsense mutations in PKD1 or PKD2. That proportion puts the number of U.S. patients with these mutations at about 40,000 to 50,000, the group EXPRESS was designed to target. Restricting the trial to specific mutations means its results will be interpreted in the context of this genetic group, not as evidence of the treatment’s effect in all patients with polycystic kidney disease. Zorblisa has received orphan drug designation for ADPKD in the United States, in addition to the designation previously announced in Europe. The designation describes the program’s regulatory status and does not by itself establish a therapeutic benefit.
The program’s background rests on preclinical results published in a peer-reviewed journal, which the company said showed restoration of full-length polycystin-1 protein production in cells carrying nonsense mutations in PKD1, with partial correction of disease-related signaling pathways. Eloxx also conducted a small, open-label Phase 2 trial in three patients with Alport syndrome between January 2023 and April 2024. The company said biopsy images showed improvement in all three patients, but the trial was not designed to establish statistical significance for efficacy. These findings provide research context for Zorblisa’s development, while the EXPRESS study is testing the drug in ADPKD and a specific genetic subgroup. The company reported cash and equivalents of $62 million on June 30, 2026, and said the amount is expected to fund its planned operations through data readouts for its Alport and ADPKD programs.