First in vivo CRISPR medicine administered to patients in clinical trial
On 4 March 2020, the collaborating companies Allergan plc and Editas Medicine, Inc. announced the dosing of the first patient with the CRISPR-based medicine AGN-151587 (EDIT-101) in a phase 1/2 clinical trial (BRILLIANCE trial).
Treatment for Leber Congenital Amaurosis 10
AGN-151587 (EDIT-101) is an experimental CRISPR-based medicine currently under development. The medicine is delivered via sub-retinal injection under development for the treatment of Leber congenital amaurosis 10 (LCA10). LCA is inherited form of blindness caused by mutations in the gene coding for the protein 290 (CEP290).
Leber congenital amaurosis (LCA) is a group of inherited retinal degenerative disorders caused by mutations in a growing group of genes. The most commonly affected genes are CEP290, GUCY2D, CRB1, RPE65, RDH12, RPGRIP1, and AIPL1. LCA is associated with severe visual impairment within the first year of life and is the most common cause of inherited childhood blindness. The prevalence of LCA is between 1/50,000 and 1/33,000 live births and accounts for 5 percent of all retinal dystrophies and 20 percent of blindness in school-age children. The most common form of the disease, LCA10, is caused by mutations in the CEP290 gene and is the cause of disease in approximately 15-20 percent of all LCA patients.
The BRILLIANCE clinical trial
TThe BRILLIANCE clinical trial is a Phase 1/2 study to evaluate the safety, tolerability, and efficacy of AGN-151587 in approximately 18 patients diagnosed with LCA10. Additional patient enrollment to the BRILLIANCE Clinical Trial is ongoing. Up to five cohorts of patients across three dose levels are planned to be enrolled in the open label, multi-center clinical trial. Both adult and pediatric patients (ages 3-17) with a range of baseline visual acuity assessments are eligible for enrollment. Patients will receive a single administration of AGN-151587 via subretinal injection in one eye. Additional details can be found on clinicaltrials.gov.
Cynthia Collins, president and CEO of Editas Medicine, commented on the groundbreaking nature of the treatment:
“This dosing is a truly historic event – for science, for medicine, and most importantly for people living with this eye disease. The first patient dosed in the BRILLIANCE clinical trial marks a significant milestone toward delivering on the promise and potential of CRISPR medicines to durably treat devastating diseases such as LCA10. We look forward to sharing future updates from this clinical trial and our ocular program”
Mark Pennesi, M.D., Ph.D., Associate Professor of Ophthalmology, Kenneth C. Swan Endowed Professor, Division Chief, Paul H. Casey Ophthalmic Genetics, Casey Eye Institute, Oregon Health & Science University, Principal Investigator and enrolling physician of the first patient treated with AGN-151587, said:
“Our first treatment in this clinical trial is an important step toward bringing new and promising treatments to patients with disease-causing gene mutations. OHSU is honored to be involved in this effort to address previously untreatable diseases such as Leber congenital amaurosis 10”
In summary, the study represents a key milestone in gene therapy and has the potential to serve as clinical proof of concept for in vivo administered CRISPR-based medicines.
 Kondkar AA and Abu-Amero KK. Leber congenital amaurosis: Current genetic basis, scope for genetic testing and personalized medicine. Exp Eye Res. 2019 Dec;189:107834. doi: 10.1016/j.exer.2019.107834. Epub 2019 Oct 19.
 https://www.orpha.net (Orpha#: 65)
 www.clinicaltrials.gov (NCT#03872479)