Gene Therapy Improves Vision in Rare, Inherited Eye Disorder

TOPLINE:

A single dose of EDIT-101, a CRISPR-associated protein 9 (Cas9)-based gene-editing therapy, appears safe and improves vision and sensitivity to light in patients with retinal disease associated with mutations in the CEP290 gene.

METHODOLOGY:

• The BRILLIANCE study evaluated the safety and efficacy of single escalating dose of EDIT-101 in patients with CEP290-associated inherited retinal degeneration, a condition where the light-sensing cells in the eye, ie, rods and cones, are disorganized and rod cells die early.

• Overall, 12 adults (median age, 37 years) and two children (age, 9 and 14 years) who were on oral prednisone for three days received a subretinal injection of EDIT-101 in the eye with the worse vision.

• Adult patients received low, intermediate, or high doses (6 × 10¹¹, 1 × 10¹², and 3 × 10¹² vector genomes/mL, respectively) of EDIT-101, while the children received only intermediate doses.

• The primary outcome was safety, which included adverse events related to treatment and the procedure, as well as toxicity that limited dosing.

• The secondary efficacy outcomes were changes in visual acuity; retinal sensitivity to blue, red, and white light; visual function navigation; and vision-related quality of life.

TAKEAWAY:

• After a median follow-up of 376 days, 22 ocular adverse events occurred, none of which was serious or dose-limiting.

• Overall, 79% of patients showed improvement in at least one efficacy outcome, and 43% improved in two or more outcomes. 

• The improvements began at month 3 and continued during follow-up visits.

• Overall, 29% of patients had meaningful improvements in visual acuity and visual function navigation, and 43% reported gains in retinal sensitivity and vision-related quality of life.

IN PRACTICE:

“These data provide proof of concept of the therapeutic potential of in vivo retinal gene editing and support further research into CRISPR-Cas9–mediated therapies for certain other inherited retinal degenerations and inherited diseases,” the authors wrote.

SOURCE:

Eric A. Pierce, MD, PhD, from the Ocular Genomics Institute in the Department of Ophthalmology at the Massachusetts Eye and Ear and Harvard Medical School, Boston, led the study, which was published online on May 6, 2024, in The New England Journal of Medicine.

LIMITATIONS:

This study was limited by the absence of a sham control, small sample size, and open-label design.

DISCLOSURES:

This study was supported by Editas Medicine, the National Institutes of Health, and other sources. Five authors declared being current or former employees or holding stock options of Editas Medicine. The other authors reported ties with many sources, including Editas Medicine.