First pediatric patient dosed in LCA10 gene editing clinical trial

This week, Editas Medicine Inc. announced the administration of EDIT-101, an experimental CRISPR gene editing medicine, to the first pediatric patient enrolled in the Brilliance clinical trial, which is designed to test the safety of EDIT-101 for the treatment of Leber congenital amaurosis 10 (LCA10), a CEP290-related group of inherited retinal degenerative disorders caused by mutations in at least 18 different genes. It is the most common cause of inherited childhood blindness, with an incidence of two to three per 100,000 live births worldwide.

According to the company, this marks the world’s first in vivo dosing of a pediatric patient with a CRISPR gene editing experimental medicine.

“Administering the experimental medicine to the first pediatric patient in the BRILLIANCE trial marks a significant milestone toward delivering on the potential of CRISPR gene editing medicines being safe and effective in treating LCA10, which often results in significant vision loss and blindness early in life,” James C. Mullen, chairman, president, and CEO, Editas Medicine, said in a statement. “Currently, there are no approved treatments for LCA10, and we look forward to sharing future updates from the BRILLIANCE trial, including sharing additional clinical data, later this year.”

EDIT-101 is a CRISPR/Cas9-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10), a CEP290-related retinal degenerative disorder. EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells. EDIT-101 has been granted Rare Pediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) and Orphan Designation from the European Medicines Agency (EMA).

The company noted that its Briliance Phase 1/2 clinical trial (NCT03872479) of EDIT-101 for the treatment of Leber congenital amaurosis 10 (LCA10) is designed to assess the safety, tolerability, and efficacy of EDIT-101 in patients with this disorder. Clinical trial sites are enrolling up to five cohorts testing up to three dose levels in this open label, multi-center study. Both adult and pediatric patients (3 to 17 years old) with a range of baseline visual acuity assessments are eligible for enrollment. Patients receive a single administration of EDIT-101 via subretinal injection in one eye. Patients are monitored every three months for a year after dosing and less frequently for an additional two years thereafter.

“Enrolling this first pediatric patient in the Brilliance trial is an important step toward bringing potentially life-changing treatments to children with genetic retinal diseases,” Tomas S. Aleman, MD, the Irene Heinz-Given and John LaPorte Research Associate Professor at the Scheie Eye Institute of the Perelman School of Medicine at the University of Pennsylvania, and a retinal degeneration specialist with the Division of Pediatric Ophthalmology at Children's Hospital of Philadelphia (CHOP), said in a statement. “We are excited to be involved in research focused on testing potential new treatments for untreatable diseases like LCA10.”

Aleman also is the trial principal investigator for the site.

Albert M. Maguire, MD, the F.M. Kirby Professor of Molecular Ophthalmology at Penn and a member of the Center for Advanced Retinal and Ocular Therapeutics, is the surgeon in the trial, in collaboration with Children’s Hospital of Philadelphia (CHOP), the nation's first hospital devoted exclusively to the care of children and the source of many breakthroughs and firsts in pediatric medicine. CHOP’s Clinical In Vivo Gene Therapy (CIGT) program provided the clinical operations support to conduct the work at CHOP.

According to the company, it initiated enrollment in the pediatric mid-dose cohort in the BRILLIANCE trial following the Independent Data Monitoring Committee (IDMC) endorsement based on an analysis of safety data from a clinical trial in adult patients that tested low-dose and mid-dose levels of the experimental medicine. The Company remains on track to complete testing of the pediatric mid-dose in the first half of 2022 and expects to initiate testing of the pediatric high-dose this year.

Previously, Editas Medicine completed dosing of all adult cohorts in its BRILLIANCE study and announced preliminary EDIT-101 clinical results demonstrated a favorable safety profile and encouraging signals of clinical benefit. The Company expects to provide a clinical update on the BRILLIANCE trial in the second half of 2022.

The update is expected to provide safety and efficacy assessments on all adult patients who have had at least six months of follow-up evaluations, which will include at least 12 months of data on the adult mid-dose cohort, and at least six months of data on the adult high-dose cohort. Additionally, the Company is expanding enrollment in one or more of the previously completed adult cohorts to explore dose response and support establishment of registrational trial endpoints, which are anticipated by year-end.