The FDA has agreed to Atsena Therapeutics’ request to expand the ongoing LIGHTHOUSE clinical study evaluating ATSN-201, its investigational gene therapy candidate, to treat X-linked retinoschisis (XLRS).
Let’s take it from the top: Why would Atsena want to expand this study?
The phase 1/2 trial’s expansion will enable it to become a continuous phase 1/2/3 pivotal trial—which would allow its clinical data to be used to support a Biologics License Application (BLA) submission to the FDA.
That’s pretty significant. Now back up and refresh me on all things Atsena.
We’ll start with Atsena itself—a Durham, North Carolina-based clinical-stage gene therapy company developing novel, next-generation treatments for the following inherited forms of blindness:
- XLRS
- GUCY2D-associated Leber congenital amaurosis (LCA1)
- MYO7A-associated Usher syndrome (USH1B)
Next up: Atsena’s next-generation, adeno-associated virus (AAV) technologies, which feature novel, laterally-spreading capsids, dual vectors, and intravitreal capsids.
- What this dual vector technology does: The dual vectors deliver larger payloads for genetic mutations that are too large to treat with a single AAV vector
- Check out a visual of how it works
And how does ATSN-201 come into play?
Currently under development for both XLRS and USH1B, the gene therapy candidate is administered as a subretinal injection.
A major piece to this: ATSN-201 utilizes AAV.SPR, one of Atsena’s novel capsids that holds a key role in treating XLRS.
How does AAV.SPR work?
The capsid spreads laterally beyond the subretinal injection site (bleb margins) to safely deliver retinoschisin (RS1) to photoreceptors within the central retina/fovea.
- Keep in mind: RS1 is a protein secreted primarily by photoreceptors that, when mutated, causes XLRS.
And what’s so special about this mechanism of action?
The AAV.SPR vector has the potential to regulate therapeutic levels of gene expression in photoreceptors to restore retinal structure and function in XLSR patients.
Nice … and didn’t ATSN-201 receive a few FDA designations recently?
Indeed it did—four, in fact, over the last year or so.
- Regenerative Medicine Advanced Therapy (RMAT; April 2025)
- Fast Track (March 2025)
- Orphan Drug (September 2024)
- Rare Pediatric Disease (August 2024)
Read up on each (above) for their significance.
Now in regards to this LIGHTHOUSE trial—give me the rundown on it.
Originally initiated in 2023 with plans to conclude in 2028, this open-label, dose-escalation, and dose-expansion trial (NCT05878860) has enrolled 21 male patients (aged 6 to 64) diagnosed with XLRS.
Its setup involves four cohorts based on patient age: ≥ 18 to < 65 years for Cohorts 1-3; age ≥ 6 to < 18 years for Cohort 4—and administered dose of ATSN-201:
- Cohort 1: Low dose
- Cohort 2: High dose
- Cohort 3: Divided into three subgroups
- Experimental: High dose and high volume
- Experimental: Low dose and low volume
- Control: No intervention
- Cohort 4: High dose (pediatric)
Didn’t the company release new findings from this?
Yup, in May 2025. The data was based on Part A of the study—which involved just the first three cohorts (with three patients in each)— and the following measurement outcomes (from baseline):
- Primary: ATSN-201’s safety and tolerability; treatment-emergent adverse events (TEAEs)
- Secondary: Changes in best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and contrast sensitivity (see here for more)
And the data thus far?
ATSN-201 was found to be safe and well tolerated; demonstrated efficacy across all dose levels; and resulted in “statistically significant improvements” for both BCVA and LLVA.
- Check out our coverage (which includes plans for Part B of the study).
So! What do we know about this trial expansion?
Atsena shared that the FDA agreed to the trial’s "proposed study design, endpoints, and patient population to support potential registration.”
The setup: An additional cohort will be added to the study (Cohort #5) with an estimated 30 adult and pediatric patients randomized 1:1 between treatment and control groups.
- After 1 year, patients in the control group will be permitted to receive treatment
And the planned assessments?
As with the study’s initial data analysis, safety and efficacy will be evaluated in all patients via measurements such as:
- Microperimetry
- Visual acuity
- Macular structure
Last question: What’s the timeframe for this expansion?
Enrollment for this new cohort is expected to begin in Q1 2026, with a pivotal data readout anticipated by the second half (H2) of 2027.
And in the long term: Atsena intends to use the findings from this expansion to support a potential Biological License Application (BLA) filing for ATSN-201 in early 2028 (pending all goes to plan).
- The potential: For ATSN-201 to become the first FDA-approved treatment for XLRS.