About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a paper published today in the New England Journal of Medicine.
โThis trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration,โ said Mark Pennesi, M.D., Ph.D., a corresponding author on the paper, an ophthalmologist and Oregon Health & Science Universityโs lead scientist for the Phase 1/2 BRILLIANCE trial. โThere is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights.
โWhile these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision.โ
The BRILLIANCE trial evaluated the safety and effectiveness of EDIT-101, an experimental gene editing treatment developed by Editas Medicine that uses CRISPR technology. The experimental treatment was designed to edit a mutation in the CEP290 gene, which provides instructions to create a protein that is critical for sight.
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People with this gene mutation have a rare condition that is commonly called Leber Congenital Amaurosis, or LCA, Type 10, for which there is currently no Food and Drug Administration-approved treatment. LCAโs various types occur in about 2 or 3 out of 100,000 newborns.
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The OHSU Casey Eye Institute treated the trialโs first participant in early 2020. That procedure also marked the first time that CRISPR had been used to edit genes within the human body, called in vivo gene editing.
The new paper describes the studyโs findings through February 2023 and details how the trialโs 14 participants โ 12 adults and two children โ responded to receiving EDIT-101 in one eye. Key results include:
- 11 participants, about 79%, showed improvement in at least one of four measured outcomes.
- 6 participants, about 43%, showed improvement in two or more outcomes.
- 6 participants, about 43%, reported improved vision-related quality of life.
- 4 participants, about 29%, had clinically meaningful improvement in visual acuity, or how well they could identify objects or letters on a chart.
- There were no serious adverse events related to the treatment.
- Most adverse events were mild or moderate, and all have since been resolved.
Four specific outcomes were used to evaluate the experimental treatmentโs effectiveness:
- Visual acuity
- How well participants saw colored points of light while looking into a specialized device, which scientists call a full-field test
- How well participants navigated a research maze with physical objects and varying amounts of light
- How much participants reported experiencing improved quality of life
Further research for a future treatment
In November 2022, trial sponsor Editas Medicine announced that it was pausing the trialโs enrollment and would seek another partner to continue the experimental therapyโs development. Pennesi 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 impacts on activities of daily living.
โThis research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,โ said Mass Eye & Ear ophthalmologist Eric Pierce, M.D., Ph.D., who is also a corresponding author. โWhile 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 โ 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.โ
โOur patients are the first congenitally blind children to be treated with gene editing, which significantly improved their daytime vision,โ said the paperโs third corresponding author, Tomas S. Aleman, M.D., a pediatric ophthalmologist at the Childrenโs Hospital of Philadelphia and the University of Pennsylvaniaโs Scheie Eye Institute. โOur hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision. This trial represents a landmark in the treatment of genetic disease, in specific genetic blindness, by offering important alternative treatment when traditional forms of therapy, such as gene augmentation, are not an option.โ
โThe results from the BRILLIANCE trial provide proof of concept and important learnings for the development of new and innovative medicines for inherited retinal diseases. Weโve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes,โ said Editas Medicine Chief Medical Officer Baisong Mei, M.D., Ph.D.
IMAGE CREDIT: NASA.
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