ARVO 2023: Treatment research for GUCY2D associated Leber congenital amaurosis type 1

Christine Kay, MD, discussed research for the treatment of GUCY2D associated Leber congenital amaurosis type 1 at this year's ARVO meeting held in New Orleans.

Video transcript

Editor’s note: Transcript lightly edited for clarity.

Christine Kay, MD:

Hello, my name is Christine Kay, I'm a vitreoretinal surgeon and inherited retinal disease specialist at Vitreo Retinal Associates in Gainesville, Florida. I'm the Clinical ophthalmology advisor for Atsena Therapeutics. I'm excited to be here in New Orleans and ARVO in 2023 to present positive safety and efficacy six months results from the Atsena Therapeutics sponsored gene therapy clinical trial for treatment of GUCY2D associated Leber congenital amaurosis type 1.

Leber congenital amaurosis is a group of autosomal recessive diseases causing blindness in children. LCA-1 is caused by two mutations in the GUCY2D gene and leads to severe visual loss. However, patients retain relatively normal retinal structure making this a good target for ocular gene therapy.

ATSN-101 is an investigational gene therapy product being developed to deliver a functional copy of human GUCY2D to photoreceptor cells. It is delivered via pars plana vitrectomy and a subretinal injection. In the ongoing Phase 1/2 clinical trial, there were positive improvements seen and visual function in patients treated at the highest dose. In total there were 15 patients treated in this trial, 3 of which were pediatric patients.

In Part A, there was a typical dose escalation done in 9 adults with the highest dose of 1.0 x 10^11 being chosen to move forward into Part B expansion with an additional 3 adults and 3 pediatric patients treated at that highest dose. Of the 9 patients who received that highest dose, there were clinically significant improvements seen in full field stimulus testing.

When comparing change from baseline and treated eyes versus untreated eyes. Best-corrected visual acuity had a positive trend, and there were no patients in the trial that lost visual acuity. There were actually two patients with baseline hand motion vision that had a greater than 0.3 logMAR visual acuity improvements. The Spark Therapeutics multi-luminance mobility test was evaluated in 5 of the high dose patients. Four of the 5 of these patients either achieved a score maximum level of 6, or had a greater than or equal to 2 score level step improvement, which has historically been seen to be clinically significant and an approvable endpoint. From a safety standpoint, there were no drug-related ocular SAEs. Ocular inflammation to date has been infrequent, minimal and reversible with steroids.

It is my great pleasure to be able to stand here today and provide positive safety and efficacy six-month results from the Phase 1/2 Atsena Therapeutics gene therapy trial for the treatment of GUCY2D associated Leber congenital amaurosis type 1. Thank you.