June 22, 2026 —
Atsena Therapeutics announced that the first patient has been dosed in the Phase 3 pivotal cohort of the LIGHTHOUSE trial evaluating ATSN-201, an investigational gene therapy for X-linked retinoschisis, or XLRS.
The company expects to complete enrollment in the pivotal cohort by the end of the first quarter of 2027, with topline results anticipated in the first half of 2028. Atsena is targeting a Biologics License Application filing in the second half of 2028.
XLRS is a monogenic X-linked inherited retinal disease caused by mutations in the RS1 gene, which encodes retinoschisin, a protein secreted primarily by photoreceptors. The disease causes abnormal splitting of retinal layers, known as schisis, leading to impaired visual acuity, progressive vision loss, and eventual blindness. XLRS primarily affects males and is often diagnosed in early childhood. There are currently no approved treatments.
ATSN-201 is designed to deliver a functional RS1 gene using AAV.SPR, Atsena’s novel laterally spreading AAV capsid. The capsid is engineered to spread beyond the subretinal injection site, enabling efficient transduction of the central retina while avoiding the surgical risks associated with foveal detachment.
The Phase 3 pivotal portion of LIGHTHOUSE is enrolling 76 patients with XLRS, including adults and children as young as six years old, across leading medical centers in North America and Europe. Patients are randomized approximately 1:1 to receive ATSN-201 or enter a control arm that will be observed for 12 months before being offered treatment.
The primary endpoint is change in microperimetry at 52 weeks, aligned with both the U.S. FDA and the European Medicines Agency. Key secondary endpoints include visual acuity and optical coherence tomography-based measures of retinal structure.
The pivotal study is supported by Phase 1/2 data showing preliminary evidence of efficacy and safety. According to Atsena, the majority of treated patients demonstrated improvements in retinal structure, including closure of foveal schisis cavities, as well as meaningful improvements in retinal and visual function measured by microperimetry, best-corrected visual acuity, and low-luminance visual acuity. These improvements have remained durable through at least one year of follow-up.
AAV.SPR is designed to address a key limitation of conventional subretinal AAV delivery. In preclinical non-human primate studies, AAV.SPR promoted transgene expression beyond the original subretinal injection bleb margins, while benchmark AAV vectors remained confined to the bleb area. At clinically relevant doses, the capsid efficiently transduced foveal cones without requiring surgical detachment of the fovea.
ATSN-201 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA, as well as Orphan Designation from the EMA. The LIGHTHOUSE trial is actively enrolling, and early enrollment progress suggests strong interest from clinicians and patients in a disease with significant unmet need.
If successful, ATSN-201 could become a potential first approved treatment for XLRS and may help establish laterally spreading AAV capsids as a differentiated approach for retinal gene therapy.
