RARE Daily

Editas Pauses First CRISPR Program in LCA Due to Small Population and Seeks Partner

November 17, 2022

Editas Medicine reported clinical data from the first trial evaluating the safety and efficacy of its experimental in vivo gene editing medicine EDIT-101 for the treatment of Leber Congenital Amaurosis, which demonstrated a favorable safety profile across all dose cohorts and achieved proof of concept.

Photo: Gilmore O’Neill, president and CEO at Editas Medicine

The trial also identified the responder population—three out of 14 patients who were homozygous for the mutated allele. In view of the small patient population, Editas said it was pausing enrollment in the study and seeking a collaboration partner to continue its development.

Leber Congenital Amaurosis, or LCA, is a 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 approximately three per 100,000 live births worldwide. Symptoms of LCA appear within the first years of life, resulting in significant vision loss and potentially blindness. The most common form of the disease, LCA10 or a CEP290-related retinal degenerative disorder, is a monogenic disorder caused by mutations in the CEP290 gene and is the cause of disease in approximately 20 to 30 percent of all LCA patients.

EDIT-101 is a CRISPR/Cas9-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10), by deleting the IVS26 CEP290 mutant allele. EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells.

The BRILLIANCE phase 1/2 clinical trial of EDIT-101 for the treatment of LCA10 is designed to assess the safety, tolerability, and efficacy of EDIT-101 in up to 34 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.

The update of the BRILLIANCE study includes safety and efficacy data from all 14 patients treated in the study to date, which includes 12 adult patients and two pediatric patients.

Three out of 14 treated subjects met a responder threshold having experienced clinically meaningful improvements in best corrected visual acuity (BCVA) and demonstrated consistent improvements in two of the following three additional endpoints: full field sensitivity test (FST), visual function navigation course (VFN), or the visual function quality of life (VFQ).

An examination of baseline characteristics of the treatment responder patients revealed that two of the three responders were homozygous for IVS26 mutation (100 percent of the homozygous patients treated). No other baseline characteristics that could pre-select a responder patient population were identified in the BRILLIANCE dataset.

EDIT-101 was tolerated with no ocular serious adverse events or dose-limiting toxicities observed. Most adverse events were mild and expected for subretinal delivery.

Since LCA10 patients homozygous for CEP290 IVS26 mutation represent an estimated population of approximately 300 in the United States, Editas said it will not progress this program independently, and will seek to identify a collaboration partner to continue the development of EDIT-101. The company said it will continue long term follow-up of all patients who have been treated to date.

“The results from the BRILLIANCE trial provide a proof of concept and important learnings for our inherited retinal disease programs,” said Gilmore O’Neill, president and CEO at Editas Medicine. “We’ve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes.”

EDIT-101 has been granted Rare Pediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration and Orphan Medicinal Product designation from the European Medicines Agency.

Author: Rare Daily Staff

Stay Connected

Sign up for updates straight to your inbox.