Editas Reports Positive Initial Data from Phase 1/2 Trial of In Vivo Gene Editing Therapy for LCA

Editas Medicine reported positive initial data from its ongoing trial of EDIT-101, its experimental in vivo gene editing therapy for a form Leber congenital amaurosis, an inherited retinal degenerative disorder.

Photo: Lisa Michaels, executive vice president and chief medical officer of Editas Medicine

The data, including preliminary patient safety and efficacy assessments relating to potential clinical benefits, were presented in an oral presentation at the 19th International Symposium on Retinal Degeneration.

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-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10). EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells.

“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,” said Mark Pennesi, professor of Molecular and Medical Genetics, Kenneth C. Swan Endowed Professor of Ophthalmology, Paul H. Casey Ophthalmic Genetics Division Chief, Casey Eye Institute, Oregon Health & Science University, and a BRILLIANCE principal investigator.

The BRILLIANCE phase 1/2 clinical trial of EDIT-101 for the treatment of LCA10, a CEP290-related retinal degenerative disorder, is designed to assess the safety, tolerability, and efficacy of EDIT-101 in up to 18 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.

Early observations from individuals who were treated in the mid-dose cohort show clinical evidence that gene editing has occurred, demonstrated by visual improvements, as measured by full-field light sensitivity threshold testing, best corrected visual acuity, or improvement in their ability to navigate standardized navigation courses with varying levels of difficulty. Editas said it will continue to follow the trial participants prospectively and collect clinical measures to allow it to determine the extent of both continued and durable improvements.

Safety data was reported with respect to all six subjects treated in the low dose and mid-dose cohorts. Most adverse events were mild and primarily resulting from the surgical procedure and subretinal injection. There were no dose limiting toxicities defined as a vision-threatening toxicity or severe non-ocular adverse event that occurs before or at the Week 4 visit and is assessed by the investigator as being related to EDIT-101 and not the administration procedure.

Mild anterior chamber inflammation was observed, and adequately controlled with oral steroids. No Cas9-specific antibody or T-cell response was detected. To date, no treatment-related cataracts, edema, or retinal thinning have been observed.

“The preliminary results shared today support our belief that EDIT-101 has the potential to provide meaningful benefits to people living with CEP290-related retinal degeneration or LCA10,” said Lisa Michaels, executive vice president and chief medical officer, Editas Medicine. “A positive safety profile has been observed through up to 15 months, with mostly mild adverse events primarily related to the procedure of retinal injection. The safety profile has allowed us to start enrolling and treating subjects in both the high-dose adult cohort and the mid-dose pediatric cohort.”

Author: Rare Daily Staff