First Patient Dosed With LCA5 Gene Therapy


Opus Genetics plans to add a pediatric cohort to the phase 1/2 trial once safety is established in adults.

Opus Genetics has dosed the first patient with Leber congenital amaurosis resulting from biallelic mutations in the LCA5 gene (LCA5) with the gene therapy OPGx-LCA5 in its phase 1/2 clinical trial (NCT05616793).1

“Dosing our first patient establishes Opus as a clinical-stage company and is a point of progress in our mission to advance first-in-class gene therapies for inherited retinal diseases,” Ben Yerxa, PhD, chief executive officer, Opus, said in a statement.1 “Despite the severe retinal dysfunction in patients with LCA5, preclinical data suggest an opportunity for therapeutic intervention, including retinal structural and functional restoration when OPGx-LCA5 was administered prior to peak disease severity. We look forward to progressing the trial of this potentially transformative therapy for patients affected by LCA5.”

The open-label, dose-escalation trial is evaluating the subretinal delivery of OPGx-LCA5 in 9 adult patients with LCA5 for safety and preliminary efficacy. Specifically, primary outcomes include dose limiting toxicities, adverse events related to the therapy or procedure, and change in retinal thickness; and secondary outcomes include retinal sensitivity by full-field stimulus testing, best corrected visual acuity, oculomotor control and fixation stability, dark-adapted transient pupillary light reflexes, and change in visual functioning questionnaire. There will be 3 doses evaluated in 3 dose groups. Once safety in adults has been established, Opusplans to add a pediatric cohort.

READ MORE: X-Linked Retinoschisis Gene Therapy Trial Doses First Patient

Opus also recently announced preclinical data supportingother AAV gene therapy candidates for RDH12-associated LCA and MERTK-associated retinitis pigmentosa. Opus conducted an observational study in 19 patients with homozygous or compound heterozygous mutations in RDH12 and found retinal regions with clearly detectable photoreceptors and signals distal to the photoreceptor inner segment despite severe retinal degeneration and vision impairment, which may benefit from gene therapy. The study was done in preparation of investigational new drug clearance-enabling studies.The company conducted another study to support the MERTK program, in which 4 MERTK plasmid constructs were evaluated for their efficiency to induce MERTK expression and which validate the plasmid’s use in gene therapy.

“Patients with inherited retinal diseases due to mutations of the RDH12 or MERTK genes experience progressive vision loss and eventual blindness, and are currently without treatment options,” Ash Jayagopal, PhD, chief scientific officer, Opus, said in an earlier statement.2 “Patients with RDH12 gene mutations have severe deterioration of the central retina; however, identification of structural-functional relationships in areas of preserved photoreceptors suggest a therapeutic window when functional restoration is possible. In addition, the ability to upregulate MERTK expression in patients with MERTK-associated retinitis pigmentosa suggests the possibility of delivering a functional MERTK gene to retinal cells to produce the normal protein. There is significant need for novel treatment options and these data further support the potential for targeted gene therapy to transform the lives of people living with inherited retinal diseases.”

1. Opus Genetics announces first patient dosed in phase 1/2 trial of gene therapy OPGx-LCA5 in patients with rare inherited retinal disease LCA5. News release. Opus Genetics. September 7, 2023.
2. Opus Genetics announces new data highlighting potential of AAV-based gene therapy for RDH12- and MERTK-associated retinal dystrophies. News release. Opus Genetics. April 26, 2023.
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