Atsena Completes Adult Dosing in XLRS Gene Therapy Trial

Atsena Therapeutics has announced the completion of adult patient dosing in Part B of the Phase 1/2/3 LIGHTHOUSE clinical trial evaluating ATSN-201, an investigational gene therapy for X-linked retinoschisis (XLRS). Pending Data Monitoring Committee approval, pediatric dosing is expected to begin in Q4 2025, marking a critical step toward broader evaluation of the therapy in younger patients.

Ongoing Evaluation of ATSN-201 in X-Linked Retinoschisis

The LIGHTHOUSE study (ClinicalTrials.gov Identifier: NCT05878860) is a multicenter, Phase 1/2/3 trial assessing the safety and efficacy of ATSN-201, a gene therapy candidate utilizing AAV.SPR, a novel laterally spreading adeno-associated virus capsid. This delivery platform is engineered to target photoreceptors in the central retina while avoiding the risks associated with foveal detachment.

According to Atsena, ATSN-201 is the first gene therapy for XLRS to demonstrate both efficacy and a positive safety profile in a clinical trial, with no serious adverse events reported up to one-year post-treatment.

Clinical Trial Design and Completion of Adult Dosing

The LIGHTHOUSE trial is divided into three sequential parts:

• Part A – Early-phase adult cohorts (1–3)

• Part B – Current adult and pediatric cohorts (4–5)

• Part C – Pivotal Phase 3 cohort (6)

In Part B, a total of nine adults and three pediatric participants are included. Adult patients were assigned to low-volume, high-volume, and control groups. Control patients will remain off-therapy for one year before becoming eligible for treatment.

The completion of adult dosing marks a significant milestone for the program.

“Dosing of adult patients in all groups of Part B is now complete, and follow-up is ongoing,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics. “Preliminary safety data remain favorable, and early structural and functional readouts, including improvements in foveal schisis and retinal sensitivity, are consistent with the positive signals observed in Part A. These findings will enable initiation of pediatric dosing, a critical next step in assessing the full therapeutic potential of ATSN-201 across the XLRS patient population.”

Regulatory Alignment and Path Toward BLA Submission

In July 2025, the U.S. Food and Drug Administration (FDA) agreed to expand the LIGHTHOUSE study to serve as a pivotal trial, supporting a potential Biologics License Application (BLA) submission targeted for early 2028.

“Completing adult dosing in Part B of the LIGHTHOUSE study represents a meaningful milestone as we advance ATSN-201 through the pivotal trial pathway,” said Patrick Ritschel, MBA, Chief Executive Officer of Atsena Therapeutics. “The FDA’s alignment on our trial design underscores the growing momentum behind this program. With no approved therapies, we remain committed to progressing this potential first- and best-in-class gene therapy as rapidly and rigorously as possible to patients with XLRS.”

Early Signs of Clinical Impact

Atsena reports that most treated patients have shown meaningful improvements in key structural and functional outcomes. These include foveal schisis closure, increased retinal sensitivity, and enhanced visual function, as measured by microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA).

These improvements, paired with a favorable safety profile, support the continued advancement of ATSN-201 into later-stage clinical development.

FDA Designations Supporting Development

ATSN-201 has received multiple regulatory designations from the U.S. Food and Drug Administration, including Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Rare Pediatric Disease, and Orphan Drug Designation. These recognitions highlight the therapy’s potential to address a significant unmet medical need in ophthalmology.