Opus Genetics has announced positive three-month data from the paediatric cohort of its ongoing Phase 1/2 clinical trial (OPGx-LCA5-1001) evaluating OPGx-LCA5, an investigational gene augmentation therapy for Leber congenital amaurosis type 5 (LCA5).
“These paediatric results are particularly exciting, as they provide evidence that OPGx-LCA5 can potentially restore cone-mediated vision in teenagers who had already experienced profound vision loss,” said Dr George Magrath, Chief Executive Officer, Opus Genetics. “These outcomes, alongside observed durable improvements observed in adults out to 18 months, give us confidence in the potential for OPGx-LCA5 to deliver meaningful and lasting benefit to patients.”
Three paediatric participants aged 16-17 with severe baseline vision impairment received a single subretinal injection of OPGx-LCA5. All three participants had improvements across multiple measures of visual function:
Visual Acuity (VA): For the paediatric cohort, early data showed a group average of a 0.3 logMAR improvement, which is greater than was observed in the adult cohort.
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- Participant 01-05 had a baseline VA of 2.2 logMAR with an improvement of 0.5 logMAR reported at one month.
- Participant 01-06 had a baseline VA of 0.96 logMAR with an improvement of 0.2 logMAR reported at three months. They reported perceiving a clear difference in brightness between their treated and untreated eyes.
- Participant 01-07 had a baseline VA of 2.3 logMAR with an improvement of 0.7 logMAR reported at one month, which was maintained through three months.
Full-Field Stimulus Testing: All three participants showed improvements in the treated eyes from one month. Participants showed >1 log unit improvement in cone sensitivity to both red and blue light. These changes provide evidence of recovery in retinal sensitivity.
Multi-Luminance Orientation and Mobility Test: All participants identified more objects through three-months compared to baseline. Two out of the three participants had greater improvement in the treated eye compared to the control eye.
Microperimetry: Two of the three paediatric participants could not conduct a microperimetry test due to their poor VA and nystagmus at screening. However, microperimetry data was obtained on one participant, for whom early signs of improved fixation stability were observed, consistent with functional retinal recovery.
These paediatric results… provide evidence that OPGx-LCA5 can potentially restore cone-mediated vision in teenagers who had already experienced profound vision loss
In addition, combined adult data support that improvements in VA were sustained through 18 months, both in terms of mean change from baseline and mean interocular difference, underscoring the potential durability of the treatment response.
Opus Genetics reported that OPGx-LCA5 has been well-tolerated in all six participants treated to date (three adults and three paediatric participants). No serious adverse ocular events or dose-limiting toxicities were observed. All ocular adverse events were mild in severity and anticipated. No events were related to the study drug. One paediatric participant had a pre-existing cataract that worsened at three months, which was attributed to the surgical procedure itself and did not obscure improvements in retinal sensitivity.
“Seeing paediatric participants achieve measurable improvements in visual acuity, retinal sensitivity, and real-world navigation tasks within three months and adult participants maintaining those improvements is a remarkable step forward,” said Dr Tomas S. Aleman, of the Scheie Eye Institute, University of Pennsylvania and principal investigator of the study. “This is important evidence supporting that gene augmentation therapy can potentially restore cone function in patients with LCA5.”
Opus Genetics plans to meet with the United States Food and Drug Administration (FDA) later this year to discuss the results and next steps.
