Editas Medicine, Inc. (NASDAQ: EDIT) has announced positive initial clinical data from an ongoing, open label Phase I/II “BRILLIANCE” study EDIT-101, a CRISPR-based experimental treatment for the treatment of Leber congenital amaurosis 10 (LCA10, due to mutations in the CEP290 gene). The study was designed to assess the safety, tolerability, and efficacy of EDIT-101 in up to 18 patients enrolling up to five cohorts testing up to three dose levels in an open label, multi-center study. Both adult and pediatric patients (3 – 17 years old) with a range of baseline visual acuity assessments were eligible for enrollment to receive a single administration via subretinal injection in one eye. Patients are monitored every three months for a year after dosing, registered on www.clinicaltrials.gov (NCT#03872479).
Preliminary results monitored safety data for six subjects treated a low dose (6×1011 vg/ml, n=2) and mid-dose (1.1×1012vg/ml , n=4) cohort. According to the company, most adverse events (AEs) “were mild and primarily resulting from the surgical procedure and subretinal injection”. There were no dose limiting toxicities or severe non-ocular AE before or at the week 4 visit. Mild anterior chamber inflammation was observed, and adequately controlled with oral steroids. No Cas9-specific antibody or T-cell response was detected and no treatment-related cataracts, edema, or retinal thinning were observed.
Efficacy was assessed based on BCVA, FST, and “visual function navigation” (developed by a CRO [Ora, Inc.]). The preliminary outcomes showed two of three subjects in the mid-dose cohort followed for up to six months having “efficacy signals suggesting productive editing and providing initial support for clinical benefits, including improvements in BCVA, FST, and/or mobility navigation”. Mid-dose cohort, with “Subject 1” showed improvement in BCVA of approximately 0.7 logMAR at month 1.5, sustained at month 6 follow-up. There was an initial positive trend toward improved FST in the study eye relative to the untreated eye. The subject also demonstrated a 5-level improvement in mobility at month 6, as assessed with the mobility assay. Mid-dose cohort “Subject 2” showed improvement by month 3 with a stable BCVA and a notable improvement in retinal sensitivity in the study eye relative to the untreated eye by FST, detectable at month 1.5 that continued to improve through month 3.
Commenting on the announcement, Mark Pennesi, M.D., Ph.D., Professor of Molecular and Medical Genetics, Casey Eye Institute, Oregon Health & Science University, and a BRILLIANCE principal investigator of the study, stated that, “I am encouraged by these initial results, which indicate this investigational gene editing treatment has been well-tolerated in this trial’s participants thus far and may also help improve sight for people with mutations in the CEP290 gene. Being able to edit genes inside the human body is incredibly profound, and I hope to be able to offer my LCA patients new treatment options involving gene editing in the future”.