Atsena reports preliminary ATSN-201 results in XLRS, including microperimetry gains, 20/40 vision in three patients and 36-month follow-up.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Atsena Therapeutics has reported preliminary safety and efficacy findings from Parts A and B of the Phase 1/2/3 LIGHTHOUSE trial (NCT05878860) evaluating investigational gene therapy ATSN-201 in patients with X-linked retinoschisis (XLRS). The data were presented at the American Academy of Ophthalmology 2026 Annual Meeting.
ATSN-201 is an investigational gene therapy using Atsena’s AAV.SPR capsid, designed to spread laterally beyond the subretinal injection site and reach the central retina. XLRS is an X-linked genetic retinal disease caused by mutations in the RS1 gene and currently has no approved disease-specific treatment.
Phase 1/2 Results
Parts A and B enrolled 21 patients, including 18 treated patients and three untreated adult controls. The treated population comprised 15 adults and three children. ATSN-201 was administered as a single subretinal injection to one eye.
Part A evaluated three dose levels in adults, while Part B evaluated different dose concentrations and injection volumes in adult and pediatric cohorts. The studies assessed retinal structure by optical coherence tomography (OCT) and visual function using microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA).
The 1.1 × 10¹⁰ vector genomes (vg)/eye dose was selected for Part C based on consistent efficacy and more favorable tolerability than higher doses. Nine patients received this pivotal dose.
Among these nine patients, seven responded on at least one visual-function measure, five showed foveal schisis closure on OCT, six were microperimetry responders, and three were visual-acuity responders. Microperimetry response was defined as an average improvement of at least 7 dB across central qualifying loci, while visual-acuity response required an improvement of at least 10 letters in BCVA or LLVA.
None of the nine untreated fellow eyes responded on OCT, microperimetry, or visual acuity.
Across all 18 treated patients, 13 responded on at least one visual-function measure. Twelve were OCT responders, nine were microperimetry responders, and nine were visual-acuity responders. Among untreated fellow eyes, one was a microperimetry responder and one was a visual-acuity responder, while none were OCT responders. None of the three untreated controls responded on OCT or microperimetry.
Three Patients Reached 20/40 or Better
Atsena also reported a new visual-acuity analysis at the pivotal dose. Eight of the nine patients had baseline acuity worse than 20/40. Three of those eight reached 20/40 or better, a level commonly used in U.S. driver’s-licensing standards. Of the remaining five patients, three improved and two were unchanged.
The finding adds a potentially patient-relevant functional outcome to the structural and retinal-sensitivity improvements observed in the study, although the small sample size limits definitive conclusions.
Three-Year Follow-Up
The earliest-treated patient reached 36 months of follow-up in July 2026 after a single ATSN-201 administration. At three years, foveal schisis remained closed, with sustained gains of +12 dB in microperimetry, +19 letters in BCVA, and +22 letters in LLVA.
Because this represents one patient’s follow-up, it provides an early durability signal rather than establishing three-year durability across the broader treated population.
Phase 3 LIGHTHOUSE Trial
Part C is the pivotal Phase 3 portion of LIGHTHOUSE, a randomized, controlled study planned to enroll 76 patients aged 5 years and older. Microperimetry at 52 weeks is the primary endpoint, with visual acuity and OCT among the key secondary assessments.
Dosing began in June 2026 at sites in the United States and United Kingdom. Enrollment is expected to finish by the end of the first quarter of 2027, with topline results anticipated in the first half of 2028 and a potential Biologics License Application filing targeted for the second half of 2028.
AAV.SPR Approach and Regulatory Status
ATSN-201 uses Atsena’s AAV.SPR capsid, designed for lateral spread from the subretinal injection site to target central photoreceptors without requiring foveal detachment.
Atsena reports that ATSN-201 has received FDA Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations, along with EMA Orphan Designation. The company also describes ATSN-201 as the first XLRS gene therapy to demonstrate clinical evidence of efficacy and safety.
These are company-reported development and regulatory claims. ATSN-201 remains investigational, and its safety and efficacy have not been established by the FDA or another regulatory authority.
What the Data Show
The October update provides preliminary evidence across multiple measures at the dose advancing into Phase 3. Six of nine pivotal-dose patients met the microperimetry response criterion, five showed foveal schisis closure, and three achieved the predefined visual-acuity response. The report of three patients reaching 20/40 or better and the 36-month follow-up in the earliest-treated patient add potentially meaningful functional and durability signals.
However, Parts A and B were small early-phase studies. The randomized Phase 3 portion of LIGHTHOUSE will be critical to determine whether these preliminary structural and functional findings translate into a reproducible treatment benefit in a larger controlled population.
Reference
Atsena Presents Positive Preliminary Safety and Efficacy Results from Parts A and B of the Phase 1/2/3 LIGHTHOUSE Trial Evaluating ATSN-201 in Patients with X-linked Retinoschisis, Atsena Therapeutics, 07 October 2026
ATSN-201 Gene Therapy in RS1-Associated X-linked Retinoschisis (LIGHTHOUSE), ClinicalTrials.gov ID NCT05878860
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.