X-Linked Retinoschisis Gene Therapy Cleared for First-in-Human Trial

Atsena anticipates initiating the Lighthouse study of ATSN-201 in mid-2023.

The FDA has cleared Atsena Therapeutics’ investigational new drug application (IND) for the gene therapy ATSN-201 to be evaluated in the first-in-human, phase 1/2 Lighthouse study in patients with X-linked retinoschisis (XLRS).1

“Intravitreally delivered AAVs have limitations, as they do not drive sufficient gene expression in photoreceptors to confer therapy and can lead to vision-compromising inflammation,” Shannon Boye, PhD, founder and director,Atsena Therapeutics, said in a statement.1 “AAV.SPR is well-suited for use in XLRS as it can drive therapeutic levels of gene expression in photoreceptors while avoiding the surgical risks of foveal detachment, which is important because XLRS patients have fragile retinas due to the presence ofschisis lesions. Building on decades of research, we’re excited to progress our novel gene therapy for patients with XLRS who currently lack an approved treatment option.”

ATSN-201, an adeno-associated virus (AAV) gene therapy, leverages Atsena’s AAV.SPR novel spreading capsid technology to safely deliver RS1 to photoreceptors in the central retina/fovea beyond the subretinal injection site. Preclinical data demonstrated that the technology promoted transgene expression beyond subretinal injection bleb margins in non-human primates, as opposed to benchmark AAVs that remain confined to original bleb margins.

“With the FDA’s clearance of the IND application for ATSN-201, we’re preparing to advance our first program utilizing AAV.SPR into the clinic for the treatment of XLRS in mid-2023,” Kenji Fujita, chief medical officer of Atsena Therapeutics.1 “We look forward to evaluating ATSN-201 and addressing the unmet need for a treatment to improve or restore vision in patients with XLRS.”

READ MORE: Luxturna Demonstrates Improvements on Multiple Vision Outcome Measures in Real-World Setting

Atsena anticipates initiating the open-label, dose-escalation Lighthouse study in male patients aged 6 to 65 years with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1 in mid-2023.

“We are really excited about dosing our first patients with [ATSN-201] probably in the next couple of months,” Fujita told CGTLive.

Atsena’s lead program candidate, ATSN-101, recently demonstrated safety and promising clinical activity in patients with Leber congenital amaurosis (LCA), due to mutations in the GUCY2D gene (LCA1) in data presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting. No serious, treatment-related adverse events were observed with only mild ocular inflammation, and improvements were observed in full-field stimulus test and multi-luminance mobility tests.2

“We had 1 patient who reported being able to see a star for the first time, which I thought was really cool. And most recently, a few weeks ago, a parent sent in a video of a patient seeing snowflakes for the first time,” Fujita told CGTLive, noting the positive patient-reported outcomes seen in the study.

1. Atsena Therapeutics receives FDA clearance of IND application for ATSN-201, an investigational gene therapy for the treatment of X-linked Retinoschisis. News release. Atsena Therapeutics. May 1, 2023. https://atsenatx.com/press-release/atsena-therapeutics-receives-fda-clearance-of-ind-application-for-atsn-201-an-investigational-gene-therapy-for-the-treatment-of-x-linked-retinoschisis/
2. Kay CN, Yang P, Cideciyan AV, et al. Six-month safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). Presented at: ARVO 2023 Annual Meeting; April 23-27; New Orleans, Louisiana. Abstract 1914
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