The CRISPR/Cas9 gene-editing therapy EDIT-101 (Editas Medicine) was well-tolerated and showed some biologic activity in patients with CEP290-associated Leber congenital amaurosis due to the c.2991+1655A>G IVS26 mutation (LCA10).1
Updated data from the BRILLIANCE trial (NCT03872479) were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana, by Eric A. Pierce, MD, PhD, William F. Chatlos Professor of Ophthalmology, Director, Ocular Genomics Institute, Harvard Medical School.
“Currently there is no treatment for severe early onset inherited retinal degeneration (IRD) caused by mutations in the CEP290 gene... The BRILLIANCE trial aims to evaluate the safety and efficacy of EDIT-101,” Pierce and colleagues wrote.1
The open-label, single ascending dose phase 1/2 BRILLIANCE trial is being conducted across 5 sites in the US and is enrolling patients with CEP290-associated IRDs at least 3 years of age. Three cohorts of adults were recruited to receive low-dose (6x1011 vg/mL), mid-dose (1x1012 vg/mL) or high-dose (3x1012 vg/mL) EDIT-101 and 1 pediatric cohort was recruited to receive mid-dose EDIT-101 in a single subretinal injection in the worse-seeing eye. Fourteen patients, with a median age of 36 years (range, 9-63) were treated. They had a mean best-corrected visual acuity (BCVA) of 2.4 logMAR (standard deviation [SD], 1.3) and 2 were homozygous for the IVS26 mutation.
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EDIT-101 had a favorable safety profile and no patients experienced any serious adverse events (AEs) related to the therapy or injection. Investigators did not identify any dose-limiting toxicities. They found that 4 participants improved in BCVA, 5 improved in full-field stimulus test (FST), and 4 improved in visual function navigation (VFN). Quality of life was also assessed, and 8 participants reported improvements. Six participants had congruent improvement in either BCVA, FST, or VFN and 3 of 5 participants that improved in an least 2 functional endpoints had up to 1.3 logMAR improvement in BCVA. Clinically meaningful endpoints were defined as at least a 0.3 logMAR change in BCVA, at least a 0.6 log cd/m2 FST score, and at least 3 points in VFN scores. For quality of life, at least a change of 4 points was considered meaningful.
“Subretinal delivery of EDIT-101 has a favorable safety profile. Efficacy data demonstrate biologic activity and provide proof of concept for in-vivo CRISPR/Cas9 gene-editing in IRDs,” Pierce and colleagues concluded.1
In other news, another of Editas' CRISPR/Cas9 therapies, EDIT-301, has received orphan drug designation for treating sickle cell disease.2 The company is expecting to report data from the phase 1/2 RUBY trial (NCT04853576) by mid-2023.