Editas Reports Results for 14 Participants in its Phase 1/2 CRISPR/Cas9 Clinical Trial for LCA10
Eye On the Cure Research News
The company is seeking a partner to move the LCA10 program forward
Editas Medicine reported that three of 14 patients (12 adults) with Leber congenital amaurosis 10 (LCA10) participating in the BRILLIANCE clinical trial for its EDIT-101 gene-editing therapy showed clinically meaningful improvements in best-corrected visual acuity (BCVA). Each of the three BCVA responders also demonstrated consistent improvements in two of the following three additional endpoints: a full field sensitivity test (FST), a visual function navigation course (VFN), or the visual function quality of life (VFQ) questionnaire. EDIT-101 is an emerging CRISPR/Cas9 gene-editing therapy for people with LCA10 caused by the IVS26 mutation in the gene CEP290. Editas is seeking a collaborative partner to further advance EDIT-101 in a clinical trial.
The EDIT-101 gene-editing technology is designed to locate and remove the IVS26 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 company found that two of the three responders in the trial were homozygous for the IVS26 mutation in CEP290 and believes these are the best patients for a future trial for EDIT-101.
Homozygous, in the context of this trial, means both versions of the patient’s CEP290 gene have the IVS26 mutation. In contrast, heterozygous means that the patient has one version of the CEP290 gene with the IVS26 mutation, but the other version has a different type of mutation.
LCA10 is an autosomal recessive disease meaning that the patient inherited one mutated version of the CEP290 gene from each parent. Recessive diseases only occur when the patient inherits two mutated versions of the gene.
In recessive diseases, parents of the affected child are usually unaffected carriers, because the parents each have one mutated version of the gene and one normal version. There is a one-in-four chance that each of their children will inherit two mutated versions of the gene, one from each parent, and therefore get the disease.
“The results from the BRILLIANCE trial provide a proof of concept and important learnings for our inherited retinal disease programs. We’ve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes,” said Gilmore O’Neill, M.B., M.M.Sc., president and chief executive officer, Editas Medicine. “While we will not progress EDIT-101 on our own and have made the decision to pause enrollment, we have the patient community top of mind and are looking for a collaboration partner to advance this program.”