Leber Congenital Amaurosis 5 Gene Therapy Cleared for Trials


OPGx-001 is the first of Opus Genetics’ gene therapy candidates for treating LCA to enter clinical trials.

The FDA has cleared Opus Genetics’ investigational new drug application (IND) of itsgene therapy for the potential treatment of Leber congenital amaurosis due to mutations in the LCA5 gene (LCA5), OPGx-001.

“We founded Opus a little more than a year ago to quickly move promising potential treatments into the clinic for patients in need. This FDA clearance of our IND application for OPGx-001 for LCA5 marks a significant milestone for Opus, as our first program to enter the clinic,” Ben Yerxa, PhD, chief executive officer, Opus, said in a statement. “Preclinical studies in in vitro and in vivo models of LCA5 have provided support for the safety and efficacy of OPGx-001. We look forward to initiating our first-in-human trial of OPGx-001 in early 2023 and to continuing to build and advance our pipeline of gene therapies for unaddressed inherited retinal diseases in parallel.”

Opus will initiate a phase 1/2 open-label, dose-escalation trial (NCT05616793) to evaluate safety and preliminary efficacy of subretinal delivery of the OPGx-001 gene therapy in early 2023. Participants must have laboratory-confirmed disease-causing biallelic LCA5 gene mutations, best corrected visual acuity (BCVA) scores of less than 20/80 on Early Treatment of Diabetic Retinopathy Study scale, have spectral domain optical coherence tomography-detectable photoreceptors, and be a good candidate for surgery. Participants who are pregnant, have complicating systemic or eye diseases, had recent intraocular surgery or investigational drug treatment, had previous gene therapy treatment, or have other conditions that would interfere with the study are excluded.

READ MORE: Leber Congenital Amaurosis CRISPR Therapy Paused for Disappointing Efficacy

The trial plans to initially enroll 9 adult patients with LCA5 to evaluate 3 doses of OPGx-001, which could be expanded to add a pediatric cohort once safety has been established in adults. The study’s primary endpoints include incidence of dose-limiting toxicities, treatment-related, or procedure-related adverse events (AEs) and change in retinal thickness. Secondary endpoints include changes from baseline to month 12 in retinal sensitivity (as measured by full-field stimulus test), BCVA, oculomotor control and fixation stability, dark-adapted transient pupillary light reflexes, and visual functioning questionnaire.

Opus Genetics’ pipeline is currently focused on addressing LCA due to different mutations with gene therapy. OPGx-001 is its lead program and the first to enter clinical trials and addresses LCA5, a severe form of early-onset LCA that leads to blindness and for which no disease-modifying therapies are currently approved. It is an adeno-associated virus 8 vector gene therapy that delivers a functionalLCA5 gene to photoreceptors in the retina. Preclinical studies in animal and human stem cell models demonstrated the therapy’s ability to preserve retinal structure and visual function prior to peak disease severity.

Opus’ other programs for LCA include the RDH12-targeting OPGx-002 and the NMNAT1-targeting OPGx-003, currently in IND-enabling studies. The programs have anticipated clinical trials planned for 2023 and 2024, respectively.

Opus Genetics receives FDA clearance of IND application for OPGx-001, a gene therapy candidate intended for the treatment of rare inherited retinal disease LCA5. News release. Opus Genetics. December 1, 2022. https://finance.yahoo.com/news/opus-genetics-receives-fda-clearance-130000056.html
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