Less than four months after the FDA cleared Atsena Therapeutics’ investigational new drug (IND) application for ATSN-201, a subretinal injection for the treatment of X-linked retinoschisis (XLRS), the company has dosed the first patient in its phase 1/2 LIGHTHOUSE trial.
Refresh me on Atsena.
Based in Durham, North Carolina, the clinical-stage gene therapy company targets the development of novel treatments for inherited forms of blindness, such as XLRS, as well as GUCY2D-associated Leber congenital amaurosis (LCA1), and MYO7A-associated Usher syndrome (USH1B).
Atsena’s next-generation, adeno-associated virus (AAV) technologies feature novel, laterally-spreading capsids, dual vectors, and intravitreal capsids.
And ATSN-201?
ATSN-201 is an investigational gene therapy candidate utilizing AAV.SPR, one of Atsena’s novel capsids, that spreads laterally beyond the subretinal injection site to ensure the safe delivery of retinoschisin (RS1)—a protein secreted primarily by photoreceptors that, when mutated, causes XLRS— to photoreceptors within the central retina/fovea.
Give me more on this novel capsid.
The AAV.SPR vector was developed to spread laterally beyond the subretinal injection bleb margins and reach therapeutic levels of gene expression in photoreceptors within the central retina
This novel vector capsid technology is designed to be conducted with minimal to none of the surgical risks associated with foveal detachment in order to potentially restore retinal structure and function
To note, the capsid is currently being investigated in both of Atsena’s XLRS and USH1B programs.
Now the LIGHTHOUSE study.
The open-label, dose-escalation, dose-expansion, randomized phase 1/2 trial (NCT05878860) is enrolling 18 male patients (Ages 6 to 64) diagnosed with XLRS caused by pathogenic or likely pathogenic mutations in the RS1 gene.
The study is being divided into four cohorts, with patient ages divided as follows:
Cohorts 1-3: age ≥ 18 and < 65 yearsCohort 4: age ≥ 6 years and < 18 years
Any other patient criteria?
Per Clinical Trials, participants must have a best-corrected visual acuity (BCVA) in both eyes of 34 to 73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (corresponding to a Snellen acuity of 20/200 to 20/40).
See here for exclusion criteria.
And the dosages?
Patients in each cohort will be subretinal administered varying injections of ATSN-201 in the following doses:
- Cohort 1
- Low dose
- Cohort 2
- High dose
- Cohort 3 (two experimental subgroups and one control subgroup)*
- Experimental: High dose and high volume
- Experimental: Low dose and low volume
- Control: No intervention
*This cohort will be partially masked.
- Cohort 4 (Pediatric)
- High dose
What’s being measured?
The primary outcome includes safety and tolerability of ATSN-201, as assessed by both dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs), from baseline to Week 52.
Secondary outcome measures, also from baseline to Week 52, includes changes in:
- BCVA
- Low-luminance visual acuity (LLVA)
- Contrast sensitivity
See here for the complete list.
When can we expect results?
Per Clinical Trials, the LIGHTHOUSE study is slated for completion in October 2029; however, data from the phase 1 (of 2, keep in mind) trial will likely be released in 2024. So stay tuned!
And the significance?
According to Atsena Chief Medical Officer (CMO) Kenji Fujita, MD, with no approved therapies currently on the market, the use of AAV.SPR in ATSN-201 ”has the potential to revolutionize the treatment of XLRS, as well as other inherited retinal disorders.”