Christine N. Kay, MD: Interim Data on ATSN-201 Shows Promise for XLRS

An update on the Phase 1/2 ATSN-201 dose escalation study reported new interim safety and efficacy data for patients with X-linked retinoschisis (XLRS) at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.

The gene therapy trial for XLRS showed improvements in both retinal structure and visual function in patients, with good safety, marking the first successful use of subretinal gene therapy for an untreatable genetic condition.

“I've now been able to refer some of my patients in my clinic to this trial because this is the first subretinal approach to XLRS,” presenter ​​Christine Kay, MD, Vitreo Retinal Associates in Gainesville, Florida told HCPLive. “I think it's promising that we have a good safety signal and a promising efficacy signal. This is really the first efficacy signal that we've seen for XLRS gene therapy.”

XLRS is a genetic disorder primarily affecting males, caused by mutations in the RS1 gene, leading to retinal layer separation and visual impairment. The trial uses ATSN-201, an adeno-associated virus (AAV)-based therapy with a novel capsid that allows broader gene delivery, aimed at correcting the defective RS1 gene in retinal cells through a one-time subretinal injection.

Interim data from the Phase ½ trial involved 6 patients treated in 2 dose groups: 3 at a low dose (1.5e10 vg/eye) of ATSN-201 and three at a high dose (5e10 vg/eye).

Safety data revealed no dose-limiting toxicities or serious adverse events (SAEs) directly related to the treatment. Mild post-surgical complications were observed, including treatable subretinal deposits in high-dose patients, prompting a dose de-escalation to an intermediate level (3e10) for the next study cohort.

Regarding efficacy, 4 of 6 patients showed closure of foveal schisis, a key anatomical improvement. Additionally, microperimetry tests indicated functional visual improvements in those with schisis closure, marking the first time gene therapy for XLRS has shown such promising efficacy.

Overall, Kay suggested this subretinal ATSN-201 approach could represent a significant step forward compared to previous intravitreal trials, with the next phase of the study currently underway.

“In conclusion, this was a dose escalation Phase 1/2 study on XLRS, a rare inherited retinal condition that causes macular schesis, which is the splitting of layers of the retina and can lead to retinal detachment in these males that are affected,” Kay added. “We had a good safety outcome, and we did see in the higher dose cohort, three events of subretinal deposits. And have decided, for our moving forward with the program to dose de-escalate to an intermediate dose [3e10 vg/eye].”

Disclosures: Kay reports an advisory role with Atsena Therapeutics.