Inside Atsena Therapeutics' Gene Therapy To Improve Functional Vision

By Erin Harris, Editor-In-Chief, Cell & Gene
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Atsena Therapeutics is a clinical-stage gene therapy company focused on developing therapies to reverse or prevent blindness. The company recently experienced positive 6-month safety and efficacy data from the ongoing Phase I/II clinical trial of ATSN-101, the company’s investigational gene therapy for the treatment of GUCY2D-associated Leber congenital amaurosis (LCA1). ATSN-101 demonstrated clinically meaningful improvements in vision at the highest dose with no drug-related serious adverse events 6 months post treatment. To learn more about ATSN-101, I caught up with Kenji Fujita, MD, Chief Medical Officer at Atsena Therapeutics. Here’s what he had to say.

Briefly describe Atsena Therapeutics and its mission. 

Atsena is a clinical stage gene therapy company, leveraging novel capsid technology uniquely suited to the eye. We have completed enrollment of an ongoing Phase 1/2 study in LCA1, are planning to initiate another Phase 1/2 clinical trial for XLRS in the coming months, and additionally are initiating IND-enabling studies for USH1B. In addition, we continue to develop and refine new capsid technologies to facilitate superior gene delivery to the eye. 

Briefly explain GUCY2D-associated Leber congenital amaurosis (LCA1). 

LCA1 is a member of a group of autosomal recessive, monogenic retinal disorders which are the leading cause of blindness in children. It is caused by mutations in the GUCY2D gene, which is an important enzyme in the phototransduction cascade. Patients present in the first months of life with severely impaired vision, but they retain healthy retinal structure throughout their lifetime, making LCA1 an ideal target for gene therapy. 

Briefly explain the investigational gene therapy ATSN-101. 

ATSN-101 is an AAV5-based gene therapy that delivers a functional copy of the GUCY2D gene to photoreceptors in the retina. The gene is linked to a photoreceptor-specific promoter to assure targeted expression. The therapy is delivered by a subretinal injection targeting the macula, the area of the retina most important for useful vision.  

Explain the findings of the Phase I/II trial. 

The trial is divided into two parts: Part A is a dose escalation phase, where we have tested 3 ascending doses in adults with LCA1. In part B, we have further explored the maximal tolerated dose in 6 additional patients; 3 adults and 3 children. We enrolled 15 patients total, ranging in age from 12 to 76 years old, and are continuing to collect data. The primary endpoint of the study is safety and tolerability. Thus far, we found that the treatment has been very well tolerated, with no drug related serious adverse events. A secondary goal is to generate exploratory data on a number of efficacy endpoints. We have seen remarkable improvements across a number of measurements. One is FST, a test which measures overall retinal light sensitivity. On this measure, we found greater than 10,000-fold improvements in some patients! This correlated with improvements in functional vision as measured by the ability to navigate a maze under low light. This is the same endpoint used for the approval of Luxturna and, excitingly, we saw improvements comparable to that shown by Luxturna in several patients.  

How might ATSN-101 impact children living with blindness? Is the intended outcome to reverse blindness? 

We are already seeing the impact on a number of patients, who have reported anecdotes of improved vision and function in their daily lives. As a couple of examples, one of our patients reported seeing a star for the first time in her life. Another was able to see snowflakes for the first time. Others reported being able to read food labels, and to cross the street safely at night with their newfound ability to see the lines of the crosswalk. We believe these examples illustrate the ability of Atsena’s gene therapy to improve functional vision in these patients and look forward to generating more data to support continued development, with the ultimate goal of making the therapy available to all eligible patients.  

What is next for Atsena Therapeutics and its ongoing clinical study? 

The primary 1-year data readout for LCA1 will occur next month. This will pave the way to discussions with the FDA on the outlines of a pivotal, Phase 3 study needed for approval. We look forward to reporting this data later this year as well as next steps toward further development.