OCU400 Appears Safe, Effective for Retinitis Pigmentosa in Phase 1/2 Update

Credit: University of Miami

OCU400 gene modifier therapy appeared clinically beneficial and safe in patients with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), according to an end-of-study Phase 1/2 update reported at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.¹

These data showed nearly 90% of patients with RP achieved stabilization or improvement of best-corrected visual acuity (BCVA) from baseline after OCU400 treatment while remaining safe, without serious adverse events (SAEs), in patients with LCA.

“OCU400 is generally safe and well-tolerated across different mutations and dose levels in RP and LCA subjects,” wrote the investigative team, led by Byron L. Lam, MD, Bascom Palmer Eye Institute, University of Miami School of Medicine.

Approximately 1.5 million people are affected by RP globally, including 110,000 in the United States, while LCA affects nearly 180,000 people worldwide.² However, treatment options for these two conditions are limited in the current armamentarium. Modern gene therapy programs address the effects of individual genes, but mutations in more than 125 genes are linked to RP and LCA.

OCU400 was designed to limit the faults of these programs, as the approach is a broad-spectrum, gene-agnostic strategy to address inherited retinal diseases (IRDs).³ The potential curative therapy includes a single subretinal injection targeting the NHR gene NR2E3.

Patients recruited for the Phase 1/2, multi-center, open-label, 3+3 dose-escalation, and dose-expansion study had RP associated with NR2E3 and RHO mutations and LCA with CEP290 mutations.¹ A total of 18 adults (11 male, 7 female) with RP received a unilateral single subretinal injection of OCU400 with low, medium, or high-dose in the study eye with worse visual acuity (VA).

Safety and efficacy endpoints were assessed at the 52-week mark. Adults and children with LCA (n = 2 each) received a medium dose of OCU400.

Upon analysis, in patients with RP, OCU400 appeared generally safe and well-tolerated across different mutations and dose levels. There were no SAEs linked to OCU400 in the low- and medium-dose cohorts. In the high-dose cohort, SAEs were reported, but not considered primarily related to OCU400 treatment.

Efficacy was assessed for 16 individuals with RP—the two individuals who experienced SAEs were not included in the efficacy analysis. A total of 13 (81%) of 16 patients experienced stabilization or improvement in BCVA, low-luminance visual acuity (LLVA), and multi-luminance mobility test (MLMT) scores in the treated eye.

Overall, Lam and colleagues indicated that OCU400 achieved treatment benefits due to stabilization in BCVA, LLVA, and MLMT.

Safety and efficacy data from 1 adult with LCA who completed 12 months and 1 adult and 2 pediatric patients who completed 9 months post-OCU400 dosing were assessed in the Phase ½ report. These data showed no SAEs related to OCU400 in patients with LCA.

“LCA subjects are currently finishing their annual 12 month visits,” they wrote. “Efficacy data like BCVA and (FST) are being collected and evaluated.”

References

1. _{Lam BL, Qamar H, Murthy Chavali VR, et al. Safety and Efficacy of OCU400 Gene Modifier Therapy for Retinitis Pigmentosa: Phase 1/2 Study Updates. Poster presented at American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}
2. _{O'Neal TB, Luther EE. Retinitis Pigmentosa. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519518/}
3. _{OCU400. Ocugen. July 26, 2024. Accessed October 15, 2024. https://ocugen.com/clinical-study/ocu400/.}