RARE Daily

Atsena Reports Positive Data from First Cohort of Trial Evaluating Gene Therapy for XLRS

May 1, 2024

Rare Daily Staff

Atsena Therapeutics reported positive preliminary data from the first cohort of the ongoing LIGHTHOUSE study, a phase 1/2 clinical trial evaluating subretinal injection of gene therapy ATSN-201 for the treatment of the rare eye disease X-linked retinoschisis.

X-linked retinoschisis (XLRS) is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood.

ATSN-201 utilizes AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment.

The LIGHTHOUSE study is evaluating ATSN-201 in male patients ages 6 and older with a clinical diagnosis of XLRS caused by mutations in the RS1 gene.

In the first (low-dose) cohort of the LIGHTHOUSE study, two of the three patients showed extensive resolution of schisis beginning at eight weeks after dosing. Additional and continued resolution of schisis was observed through week 24, the latest time point available. Notably, areas of schisis cavity resolution were found both inside and well outside of the subretinal injection blebs, indicating that AAV.SPR is spreading laterally from the injection blebs, consistent with expectations of this novel, laterally spreading capsid.

Early efficacy was also observed using microperimetry, with functional improvements seen in the same locations as structural improvements. Improvements were measured in terms of decibels (dB), a measure of light sensitivity of the retina. Improvements of up to 14 dB were seen in one patient, with 38 loci showing an improvement of greater than 7 dB. The U.S. Food and Drug Administration considers an improvement of at least 7 dB at 5 or more prespecified loci to be clinically meaningful.

ATSN-201 was well tolerated in all three XLRS patients in the first cohort and no serious adverse events were reported. These results demonstrate, for the first time, the ability to safely administer subretinal injections in patients with extensive retinal schisis.

“We’re particularly pleased to have clinical validation of AAV.SPR’s ability to spread laterally well beyond the subretinal injection blebs,” said Kenji Fujita, chief medical officer of Atsena Therapeutics. “With dosing of patients in the mid-dose cohort underway, we look forward to the swift progression of this first clinical trial utilizing our novel spreading capsid and to the continued development of our best-in-class gene therapy candidate for XLRS patients who currently lack an approved treatment option.”

Photo: Kenji Fujita, chief medical officer of Atsena Therapeutics


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