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Leber congenital amaurosis (LCA) initiates a Phase 1/2 trial for CRISPR gene therapy study following an earlier commercial success in gene therapy

Editas Medicine, Inc. (Nasdaq: EDIT), in collaboration with Allergan plc (NYSE: AGN), has announced the dosing of the first patient for LCA of a novel gene therapy CRISPR technology, called “AGN-151587 (EDIT-101)”.  AGN-151587 (EDIT-101) is an experimental medicine delivered via sub-retinal injection under development for LCA10, caused by mutations in the centrosomal protein 290 (CEP290) gene. The Phase 1/2 study is to evaluate AGN-151587 assessing the safety, tolerability, and efficacy of treatment in approximately 18 patients with LCA10.  The study, based at the Oregon Health & Science University (OHSU) Casey Eye Institute, is registered for NCT03872479 (


LCA is almost an autosomal recessive disorder counting 25 different genes, 30% of which carry various mutations in the CEP290 gene.  An estimate for the addressable AGN-151587 population may now number 2,000-5,000 patients in the USA and UK together.   CEP290 is a centrosomal protein that is localized to the connecting cilium of the photoreceptors and is involved in both ciliogenesis and ciliary trafficking while cone photoreceptors have abnormal inner and outer segments resulting in severe vision loss.  The Phase 1/2 trial has the primary endpoint with safety and adverse events and with secondary endpoints with efficacy, including visual acuity, mobility course, macula thickness, pupillometry and electroretinogram. Up to five cohorts of patients across three dose levels will be enrolled in an open label, multi-center, clinical trial with adult and paediatric patients (3 – 17 years old). CRISPR (an acronym for “clustered regularly interspaced short palindromic repeats”) is one of the latest gene-editing tools, originally uncovered as a bacterial defense mechanism against phage infection, and now under development as a potential gene therapy approach.  The technology derives from observations made in the repetitive sequences isolated from a number of prokaryotic and archaebacteria, first identified in 1987 by Yoshizumi Ishino and Atsuo Nakata, then at Japan’s Research Institute for Microbial Diseases, Osaka University.  Working on the E.coli iap enzyme, responsible for the isozyme conversion of alkaline phosphatase, Ishino and colleagues reported an unusual set of 29 nucleotide repeats interspersed with five intervening 32 nucleotide sequences, seemingly without any discernible function.  Over a period of 10+ years, as increasing numbers of DNA sequences were deposited in the public databases, and a growing number of similarly structured repeat sequences, interspersed with unusual sequence, were reported from several different bacterial and archael strains.


Commenting on the announcement, Brent Saunders, Chairman and CEO of Allergan stated that, “currently patients living with LCA10 have no approved treatment options. For years, Allergan has had an unwavering commitment to advancing eye care treatments. With the first patient treated in this historic clinical trial, we mark a significant step in advancing the AGN-151587 clinical program and move closer to our goal of developing a game-changing medicine for LCA10 patients”.