Atsena Therapeutics Publishes 12-Month Safety and Efficacy Data from Phase 1/2 Trial of ATSN-101 in LCA1

Atsena Therapeutics announced 12-month safety and efficacy results from its phase 1/2 clinical trial of ATSN-101, an investigational gene therapy for Leber congenital amaurosis (LCA1), a rare inherited retinal disease causing severe vision impairment or blindness from infancy. The findings were published today in The Lancet.

ATSN-101, developed by Atsena’s founders, Shannon and Sanford Boye, at the University of Florida, is the first gene therapy studied to treat LCA1, which is caused by biallelic mutations in the GUCY2D gene.

“There are no approved treatments for LCA1. The improvements in visual function and tolerability we saw at the high dose of ATSN-101 at 12 months post-treatment support a future phase 3 trial. This therapy represents a significant advancement in reversing blindness that begins in childhood," Dr. Artur Cideciyan, Research Professor of Ophthalmology at the Scheie Eye Institute of the University of Pennsylvania and senior author of the paper, said in a company news release.

The phase 1/2 trial involved 15 patients with genetically confirmed LCA1, who received unilateral subretinal injections to assess safety and preliminary efficacy of increasing doses of ATSN-101. Participants were treated at either the Scheie Eye Institute or Oregon Health & Science University’s (OHSU) Casey Eye Institute. Dose escalation involved three groups of adult patients receiving ascending doses of the therapy, followed by an expansion phase that included one pediatric and one adult cohort treated at the highest dose.

The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), while secondary endpoints included full-field stimulus testing (FST) and best-corrected visual acuity (BCVA), as well as a multi-luminance mobility test (MLMT). Results showed significant improvements in retinal sensitivity in high-dose subjects, with a 20.3-decibel mean change in dark-adapted FST, representing a 100-fold improvement in treated eyes. These improvements were first observed at day 28 and persisted over 12 months. Modest gains in BCVA were also noted, with an average improvement of eight letters on the eye chart for high-dose subjects at 12 months. In the MLMT, three of six high-dose patients achieved maximum scores at 12 months.

Adverse events were mostly mild (91%) or moderate (9%), with no serious events related to ATSN-101. Ocular inflammation was mild and managed with steroids.

“This is the first time patients with LCA1 have been treated with gene therapy, making this a potential first-ever treatment for the disease,” said Dr. Paul Yang, lead author and Associate Professor of Ophthalmology at OHSU. “We are excited to share these groundbreaking results with the wider medical community.”