Opus Genetics has received Rare Pediatric Disease designation (RPD) from the FDA for OPGx-LCA5, its investigational ocular gene therapy candidate, to treat patients diagnosed with Leber congenital amaurosis (LCA) resulting from biallelic mutations in the LCA5 gene.
First, a refresher on Opus Genetics.
The clinical-stage gene therapy company is headquartered in Raleigh, North Carolina and funded by the Retinal Degeneration (RD) Fund, a venture arm of the Foundation Fighting Blindness (FFB).
Its target: Addressing unmet needs found in the inherited retinal disease (IRD) space.
- How: Via an adeno-associated virus (AAV)-based gene therapy portfolio positioned to leverage novel orphan drug manufacturing scale and efficiencies for the following indications:
- LCA
- Vitelliform macular dystrophy
What’s the company been up to lately?
Aside from this major news …
In June 2024, Opus Genetics was granted almost $2 million in project-based funding to support two preclinical IRD-based gene therapy programs for:
- Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP)
- RP due to mutations in the proto-oncogene tyrosine-protein kinase MER (MERTK) gene
Gotcha. Now let’s discuss this gene therapy candidate.
The company’s most advanced clinical program, OPGx-LAC5, targets LCA5 via a single, unilateral subretinal injection.
How it works: The therapeutic uses an adeno-associated virus (AAV) vector to deliver a functional LCA5 gene to photoreceptors within the retina.
And the clinical data on it?
Per the company, preclinical data from animal and human induced pluripotent stem cells (iPSCs) of LCA5 showed visual function preservation when OPGx-LCA5 was administered before the disease reached its peak in severity.
What this suggested: An expansive therapeutic window for LCA5, Opus Genetics noted.
Isn’t there an ongoing trial evaluating the therapeutic?
Yes, actually! In fact, The FDA cleared its investigational new drug (IND) application of OPGx-LCA5 in December 2022 for a phase 1/2 first-in-human trial (NCT05616793).
- The study design: non-randomized, open-label, phase 1/2 dose-escalation study
- The participants: estimated 15 patients diagnosed with LCA5-IRD (aged 13+)
- The design: evaluating three doses of OPGx-LCA5 administered in three cohorts:
- Cohort 1: low dose: 1E10 vg/eye
- 2 adults, 3 adolescents
- Cohort 2: intermediate dose: 3E10 vg/eye
- 2 adults, 3 adolescents
- Cohort 3: high dose: 1E11 vg/eye
- 2 adults, 3 adolescents
- Cohort 1: low dose: 1E10 vg/eye
- Study duration: 12 months
And what’s being measured?
Measured at 1 year, primary outcomes include:
- Dose-limiting toxicities
- OPGx-OO1 (LCA5) adverse events (AEs)
- Procedure-related AEs
- Change in retinal thickness
- Measured via optical coherence tomography (OCT)
Secondary outcomes include:
- Change from baseline to month 12 in:
- Retinal sensitivity
- Best-corrected visual acuity (BCVA)
- Oculomotor control and fixation stability
- Transient pupillary light reflexes (TPLR)
- Visual functioning questionnaire
- Mesopic, low-contrast visual acuity (MLCVA)
See here for other outcomes.
When are results expected?
While Clinical Trials reports the primary completion (aka: the last dosing of the trial) is slated for December 2024, the study isn’t expected to conclude until January 2028.
Alrighty, now this FDA designation.
Quick refresh: A Rare Pediatric Disease Designation (RPDD) is granted by the FDA for drugs under development for rare childhood diseases (affecting patients under the age of 18) when a few key criteria have been met. See those criteria here.
And its significance?
As part of the RPDD program, OPGx-LCA5 also qualifies Optus Genetics for a priority review voucher (PRV)—eligible only once OPGx-LCA5 has been approved by the FDA.
What this also enables: The PRV could potentially allow Optus Genetics to receive an expedited 6-month priority review for any marketing applications that follow (such as an IND or new drug application [NDA]), or that can be sold or transferred to other companies (to generate additional revenue).