Atsena Therapeutics Shares 12-Month Phase I/II ATSN-101 LCA1 Trial Results in The Lancet

A clinical-stage gene therapy company, Atsena Therapeutics, has revealed promising 12-month safety and efficacy data from its Phase I/II trial of ATSN-101. This investigational gene therapy targets Leber congenital amaurosis type 1 (LCA1), caused by biallelic mutations in the GUCY2D gene. Published in The Lancet, the study signifies a significant step towards reversing blindness in patients affected by this inherited retinal disease.

LCA1 is a severe retinal disorder that causes vision impairment or blindness from infancy. There are currently no approved treatments for this condition. ATSN-101, developed by Atsena’s founders at the University of Florida, is the first gene therapy to be trialed for LCA1.

The clinical trial involved 15 patients with genetically confirmed LCA1, all receiving unilateral subretinal injections of ATSN-101. The study aimed to evaluate the safety and preliminary efficacy of increasing doses of the therapy. Thirteen patients were treated at the Scheie Eye Institute, with two others receiving treatment at Oregon Health & Science University (OHSU) under the supervision of Dr. Paul Yang and Dr. Andreas Lauer.

Patients were divided into cohorts for the dose escalation phase, receiving low, mid, and high doses of ATSN-101. In the dose expansion phase, both adults and children received the high dose. The trial's primary focus was on the incidence of treatment-emergent adverse events (TEAEs). Secondary measures included full-field stimulus test (FST) and best-corrected visual acuity (BCVA), alongside a multi-luminance mobility test (MLMT).

Dr. Artur Cideciyan, a senior author of the paper and Research Professor of Ophthalmology at the Scheie Eye Institute, emphasized the significance of these findings. He noted the improvements in visual function and tolerability observed at the high dose 12 months post-treatment, supporting the potential for a future Phase III trial.

Dr. Paul Yang, the lead author from OHSU, expressed optimism about the results, marking a historic moment as the first time gene therapy has been administered to patients with LCA1. Publication in a prestigious journal like The Lancet extends the reach of this groundbreaking work to the broader medical community.

High-dose patients showed a mean change in dark-adapted FST of 20.3 decibels, indicating a 100-fold improvement in treated eyes. These improvements were evident from day 28 and sustained over 12 months. BCVA also showed modest gains with an average improvement of -0.16 logMAR, equating to eight letters. Three of six high-dose subjects achieved the maximum MLMT score by the 12-month mark.

All adverse events were classified as mild or moderate, with 91% mild and 9% moderate. The TEAEs were consistent with those observed in other subretinal gene therapy studies, mostly related to the surgical procedure rather than the therapy itself. Mild ocular inflammation was managed effectively with steroid treatment.

Dr. Kenji Fujita, Chief Medical Officer of Atsena Therapeutics, highlighted the promise of ATSN-101 as a potential first-in-class gene therapy for LCA1. The early and persistent improvements in retinal sensitivity underscore the potential durability of this investigational therapy.

The published manuscript, titled “Safety and Efficacy of ATSN-101 in Patients with Leber Congenital Amaurosis caused by Biallelic Mutations in GUCY2D: A Phase 1/2, Multi-Center, Open-Label, Unilateral Dose Escalation Study,” will also appear in the print issue of The Lancet.

Leber congenital amaurosis type 1 (LCA1) is caused by mutations in the GUCY2D gene, leading to severe vision impairment or blindness from early childhood. It accounts for around 20% of LCA cases, with no current approved treatments. ATSN-101 introduces functional GUCY2D to photoreceptors, showing promising results in the ongoing trial.

Atsena Therapeutics, founded by pioneers in ocular gene therapy, is committed to developing treatments for inherited retinal diseases. Their lead program, ATSN-201, is under trial for X-linked retinoschisis (XLRS), another genetic retinal disorder. The company's innovative adeno-associated virus (AAV) technology aims to overcome the challenges of treating inherited retinal diseases.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!