A landmark clinical trial has demonstrated that a CRISPR-based therapy is safe and effective in the treatment of inherited retinal disorders (IRD).
The BRILLIANCE phase 1/2 trial by US-based clinical stage genome editing company, Editas Medicine, demonstrated 11 out of 14 treated participants experienced some improvements in vision and quality-of-life measures.
The trial was led by principal investigator Dr Eric Pierce, director of the Ocular Genomics Institute and Berman-Gund Laboratory for the Study of Retinal Degenerations at Mass Eye and Ear and Harvard Medical School, with the findings published in The New England Journal of Medicine.
“This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” said Dr Pierce.
“While more research is needed to determine who may benefit most, we consider the early results promising. To hear from several participants how thrilled they were that they could finally see the food on their plates – that is a big deal. These were individuals who could not read any lines on an eye chart and who had no treatment options, which is the unfortunate reality for most people with inherited retinal disorders.”
All 14 trial participants, including 12 adults (ages 17 to 63) and two children (ages 10 and 14), were born with a form of Leber Congenital Amaurosis (LCA) caused by mutations in the centrosomal protein 290 (CEP290) gene.
They underwent a single injection of a CRISPR/Cas9 genome editing medicine, EDIT-101 in one eye via a specialised surgical procedure. This trial, which included the first patient to ever receive a CRISPR-based investigational medicine directly inside the body, focused primarily on safety with a secondary analysis for efficacy.
No serious treatment or procedure-related adverse events were reported, nor were there any dose-limiting toxicities. For efficacy, the researchers looked at four measures: best-corrected visual acuity (BCVA); dark-adapted full-field stimulus testing (FST), visual function navigation (VNC, as measured by a maze participants completed), and vision-related quality of life.
Eleven participants demonstrated improvements in at least one of those outcomes, while six demonstrated improvements in two or more.
Dr Baisong Mei, chief medical officer at Editas, said the results from the BRILLIANCE trial provide proof-of-concept and important learnings for the development of new and innovative medicines for inherited retinal diseases.
“We’ve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes,” he said.
Co-author and site principal investigator Professor Tomas Aleman said the patients are the first congenitally blind children to be treated with gene-editing, which significantly improved their daytime vision.
“Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision,” he said. “This trial represents a landmark in the treatment of genetic diseases, in specific, genetic blindness, by offering an important alternative treatment, when traditional forms of gene therapy, such as gene augmentation, are not an option.”
In November 2022, Editas paused enrolment on the BRILLIANCE trial. Dr Pierce and colleagues are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. The researchers hope future studies can examine ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients and include refined endpoints to measure the effects of improved cone function on activities of daily living.
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