Atsena Therapeutics, a clinical-stage gene therapy company, is making strides in the development of ATSN-201, a gene therapy for X-linked retinoschisis (XLRS). The company announced the completion of dosing in Part A of the LIGHTHOUSE study, a Phase I/II clinical trial, and has initiated Part B of the trial. These developments mark significant milestones in the pursuit of a treatment for this inherited retinal disease that affects approximately 30,000 males in the U.S. and EU. Currently, there are no approved treatments for XLRS.
Positive Outcomes from Part A
Part A of the LIGHTHOUSE study involved nine adult patients who received subretinal injections of ATSN-201 at three different dose levels. According to Kenji Fujita, MD, Atsena's Chief Medical Officer, the results were promising. "We have seen both structural and functional benefits in patients treated at all dose levels. Additionally, no serious adverse events related to treatment have been reported," said Fujita. These findings validate the use of Atsena's novel AAV.SPR capsid for effectively treating inherited retinal diseases.
Novel AAV.SPR Capsid
ATSN-201 leverages AAV.SPR, a novel spreading capsid developed by Atsena Therapeutics. This capsid is designed to achieve therapeutic levels of gene expression in the photoreceptors of the central retina while avoiding the surgical risks associated with foveal detachment. AAV.SPR spreads laterally beyond the subretinal injection site, enabling efficient transduction of the central retina, where schisis cavities are most prevalent in XLRS patients. Preclinical studies in non-human primates have demonstrated that AAV.SPR promotes transgene expression well beyond the injection site, unlike standard AAV vectors.
Initiation of Part B
Following the successful completion of Part A, Atsena Therapeutics has initiated Part B of the LIGHTHOUSE study. This phase will enroll nine additional adults and three pediatric patients with XLRS. The adult cohort will be divided into three arms: low volume, high volume, and control. Patients in the control arm will be observed off-therapy for one year before having the option to receive treatment. The pediatric cohort will be dosed after evaluating preliminary data from the adult cohort. Part B will continue to assess the safety and efficacy of ATSN-201, including microperimetry, visual acuity, and macular structure.
The Data Monitoring Committee has recommended proceeding to Part B using a concentration of 1.0E11 vg/mL, which demonstrated an optimal balance of tolerability and efficacy based on preliminary clinical results from Part A.
XLRS: An Unmet Medical Need
XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene, which encodes retinoschisin. This protein is crucial for the structural integrity of the retina, and its deficiency leads to abnormal splitting of retinal layers, resulting in impaired visual acuity and eventual blindness. The condition primarily affects males and is typically diagnosed in early childhood. With approximately 30,000 males in the U.S. and EU affected and no approved treatments available, the need for effective therapies is significant.
Strategic Implications
Patrick Ritschel, CEO of Atsena Therapeutics, emphasized the potential impact of ATSN-201. "This marks a significant milestone for patients with XLRS as we push to bring a therapeutic option to individuals that otherwise have no approved treatment," Ritschel said. He also noted the broader potential for individuals with other inherited retinal diseases who could benefit from their novel capsid.
Kenji Fujita, MD, also highlighted a key benefit of ATSN-201: "A major benefit of ATSN-201 is that it does not need to be precisely placed underneath a specific retinal region. This gives surgeons more discretion regarding bleb placement during subretinal surgery and allows for safe delivery of the healthy gene to the critical portion of the retina."
The LIGHTHOUSE study is an ongoing Phase I/II, open-label, dose-escalation and dose-expansion clinical trial (NCT05878860) evaluating the safety and tolerability of ATSN-201 in male patients ages six and older with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. ATSN-201 has received Orphan Drug and Rare Pediatric Disease designations from the FDA.
