Preliminary adult data from Atsena’s LIGHTHOUSE trial continue to show structural and functional improvement signals in X‑linked retinoschisis alongside a favorable safety profile, with no serious adverse events reported through at least one year in earlier cohorts. In Part B, early readouts mirror Part A: reductions in foveal schisis and gains in retinal sensitivity with supportive trends in microperimetry, best-corrected visual acuity, and low-luminance visual acuity.
The company has completed adult dosing in Part B of its adaptive Phase I/II/III program evaluating ATSN‑201, a subretinal AAV gene therapy using a laterally spreading capsid designed to transduce the central retina without macular detachment. The Part B design includes three adult groups—low volume, high volume, and an off-therapy control with optional crossover at one year—plus three pediatric patients. With adult enrollment complete and preliminary data deemed supportive, pediatric dosing is slated to begin in Q4 2025 pending DMC approval. In July, the FDA agreed that the expanded study can serve as the pivotal pathway, setting up initiation of the Phase III cohort in Q1 2026 and a targeted BLA submission in early 2028.
Strategically, Atsena is pursuing speed and risk containment in a setting where historical intravitreal RS1 gene therapy efforts struggled with transduction and inflammation. The laterally spreading subretinal approach aims to reach foveal cones while avoiding surgical macular detachment, a key operational and safety constraint in inherited retinal disease trials. The adaptive, small-N design with delayed-treatment control balances ethical considerations in a pediatric, vision-threatening condition while creating a comparator window for regulatory review. RMAT, Fast Track, Orphan, and Rare Pediatric Disease designations provide additional regulatory leverage and, if ultimately approved, the prospect of a priority review voucher.
For sites, the pivot to pediatric dosing raises immediate execution questions: anesthesia workflows, pediatric vitreo‑retinal surgical capacity, and the feasibility of functional endpoint testing in younger patients. Imaging core labs and device vendors will be central, as OCT readouts of schisis closure and reliable microperimetry will need tight standardization across centers. CROs should expect heightened DMC oversight, complex crossover logistics, and long-term follow-up infrastructure typical of AAV programs. Regulators will focus on endpoint selection and durability; absent a universally accepted functional endpoint for XLRS, alignment on a composite structural/functional primary, and the magnitude of clinically meaningful change will be pivotal.
The next 12–18 months hinge on three deliverables: pediatric safety consistency with adults, evidence of durable functional benefit beyond structural normalization, and clean execution of the crossover control to support causal inference. On the CMC side, a novel capsid means process lock, potency assays, and comparability packages must be de‑risked early to keep a 2028 filing viable. Any signal of inflammation, vector shedding concerns, or variability in surgical technique could slow timelines or complicate labeling.
If the Phase III cohort reproduces the current signal across age groups with year‑over‑year durability, the program could set a regulatory precedent for XLRS and clarify acceptable endpoints for future IRD gene therapies. Watch for pediatric interim data cadence, prespecified responder thresholds, and FDA feedback on endpoint hierarchy. Site activation velocity and surgical training standardization will also telegraph whether the pivotal cohort can enroll on schedule and whether a one‑time therapy for XLRS can be operationalized beyond a handful of high‑volume centers.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
