Vision Improvements Reported for Two LCA 10 Patients in Phase 1/2 Clinical Trial for Editas’ CRISPR/Cas9 Treatment
The emerging treatment targets a specific mutation (c.2991+1655A>G in Intron 26) of the gene CEP290 which causes Leber congenital amaurosis 10 (LCA 10)
At the XIXth International Symposium on Retinal Degeneration (RD2021), Mark Pennesi, M.D., Ph.D., Oregon Health & Science University, reported that two of three participants in the mid-dose group of Editas’ BRILLIANCE Phase 1/2 clinical trial for its LCA 10 CRISPR/Cas9 treatment showed improvements in vision. Known as EDIT-101, the emerging gene-editing therapy is the first of its kind to be administered directly to the human body.
One participant in the BRILLIANCE trial had improvements in best corrected visual acuity (BCVA, the ability to read lines on an eye chart) sustained for six months and in the ability to navigate a mobility course at the sixth month after treatment. Also, the participant showed a positive trend in retinal sensitivity (as measured by a full field stimulus threshold test or FST).
Another participant had stable BCVA at three months and a notable improvement in retinal sensitivity at six weeks that continued to improve through the third month.
Dr. Pennesi said that no serious adverse events were observed. Safety data were reported for a total of six participants — two in the low dose group and four in the mid-dose group.
“We are encouraged by these early results of safety and efficacy and look forward to additional data as the trial moves forward,” said Ben Yerxa, PhD, chief executive officer at the Foundation Fighting Blindness. “CRISPR/Cas9 is a promising, emerging technology for addressing inherited retinal diseases and we are excited by its potential.”
The EDIT-101 gene-editing technology is designed to locate and remove a specific mutation (c.2991+1655A>G in Intron 26) in the CEP290 gene. The treatment works like a pair of molecular scissors to cut out the mutation. The treatment is delivered to photoreceptors by a subretinal injection.
Gene editing is different from gene (augmentation) therapy. In gene therapy, copies of an entirely new gene are delivered to the retina to replace the defective copies. In CRISPR/Cas9 gene editing, only the mutated region of the gene is corrected.
Gene-editing is an attractive approach for addressing large genes (e.g., CEP290) which exceed the cargo capacity of commonly used viral delivery systems such as adeno-associated viruses or AAVs.
The Foundation Fighting Blindness is a sponsor of the XIXth International Symposium on Retinal Degeneration in Nashville from September 27 to October 2, 2021.