Atsena Therapeutics reaches phase 3 milestone for gene therapy targeting X-linked retinoschisis
Durham-based Atsena Therapeutics, a clinical-stage gene therapy company focused on using genetic medicine to reverse or prevent blindness, has dosed the first patient in the Phase 3 pivotal cohort of the LIGHTHOUSE trial evaluating its ATSN-201 gene therapy for the treatment of X-linked retinoschisis (XLRS).
About 35,000 males in the United States and Europe have XLRS, an inherited disease that causes loss of central and peripheral vision due to retinal degeneration. It is caused by mutations in the RS1 gene, which encodes retinoschisin, a protein secreted primarily by photoreceptors.
ATSN-201 uses AAV.SPR, a novel, laterally spreading capsid designed to deliver a functional RS1 gene to photoreceptors in the central retina while avoiding the surgical risks of foveal detachment.
Since enrollment for the Phase 3 study began in May, the company has already enrolled 10% of the study and is now activating additional planned sites across North America and Europe.
“Dosing the first patient in the LIGHTHOUSE pivotal cohort is a defining moment for Atsena and for the XLRS community,” said Patrick Ritschel, the company’s Chief Executive Officer. “The speed with which we are enrolling speaks to the urgency patients and physicians have about finding a treatment for this disease.”
Atsena plans to complete enrollment by the end of the first quarter of 2027, with topline results expected in the first half of 2028, followed by a Biologics License Application (BLA) filing in the second half of the year.
Phase 3 trial design
The Phase 3 portion of the LIGHTHOUSE trial is enrolling 76 patients with XLRS, including adults and children as young as 6 in North America and Europe. Patients are randomized to receive the ATSN-201 treatment for a year or be in the control group, which is observed for 12 months and then offered the option to receive treatment.
Researchers will evaluate retinal sensitivity, visual acuity, and changes in the retina's structure to determine how well the treatment protects and improves retinal and visual function.
“We enter this pivotal study with a high degree of confidence, backed by Phase 1/2 data showing that ATSN-201 can reverse structural damage to the retina and meaningfully improve vision,” said Ritschel. “XLRS families have waited a long time for a treatment, and we intend to deliver one.”
Encouraging safety and efficacy results
Lesley Everett, M.D., Ph.D., from the Casey Eye Institute at Oregon Health & Science University, recently presented 12-month safety and efficacy results from Part A of the LIGHTHOUSE Trial at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
Part A findings included a favorable safety profile across all nine adult patients, with no drug-related serious adverse events, no dose-limiting toxicities, and no patient discontinuations. Additionally, improvements in retinal structure (foveal schisis closure) were maintained in seven of nine treated eyes at 12 months — a result not observed in untreated eyes. Statistically significant improvements in retinal and visual function were also observed in participants receiving the treatment.
ATSN-201 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease and Orphan Drug Designations from the U.S. Food and Drug Administration and Orphan Designation from the European Medicines Agency.
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