Phase 3 Trial of Gene Modifier Therapy for Retinitis Pigmentosa Ready For 2024

Ocugen has aligned with the FDA on key aspects of its proposed phase 3 trial design to further assess its gene modifier therapy, OCU400, in patients with retinitis pigmentosa (RP) caused by RHO (rhodopsin) and other gene mutations.¹

“This news brings us even closer to fulfilling our mission to bring our first-in-class, gene-agnostic therapies to market and provide access to patients globally,” Shankar Musunuri, PhD, Chairman, Chief Executive Officer, and cofounder, Ocugen, said in a statement.¹ “We look forward to beginning the Phase 3 clinical trial, which we plan to initiate in early 2024.”

Ocugen and the FDA agree on aspects of the trial including the study endpoint, patient enrollment strategy, and study duration (1 year). In comparison with the ongoing phase 1/2 clinical trial (NCT05203939), the phase 3 trial will enroll a broader group of patients with RP, including patients with the most common RHO gene mutation, to assess OCU400’s gene-agnostic mechanism of action in.

Ocugen most recently reported a data update from the phase 1/2 trial in September 2023. The updated data includes results from 12 patients who were evaluable for efficacy in cohort 1 (low dose, adults with RP), cohort 2 (medium dose, adults with RP), cohort 3 (high dose, adults with RP and adults with LCA), and the phase 2 open enrollment cohort (medium dose, adults with LCA).² The patients’ follow-up ranged from 6 months to 12 months. Among the 12 patients, 10 patients (83%) experienced stabilization or improvement from baseline in best-corrected visual acuity (BCVA) in their treated eyes. Among a subset of 7 patients who had disease associated with mutations in the RHO gene, 4 patients (57%) showed a 4-letter improvement in BCVA in treated eyes from baseline and 3 patients (43%) showed a 7-letter improvement in BCVA in treated eyes from baseline.

WATCH NOW: Shankar Musunuri, PhD, on Promising Efficacy Signals With Modifier Gene-Agnostic Therapy in Retinitis Pigmentosa

In terms of low-luminance visual acuity (LLVA), 10 of 12 patients (83%) likewise experienced stabilization or improvement from baseline in their treated eye. Among the patients with RHO mutations, 3 patients (57%) showed a 5-letter improvement in LLVA in treated eyes from baseline and 2 patients (29%) showed a 10-letter improvement in LLVA in treated eyes from baseline. The study also measured multiluminance mobility testing (MLMT) scores; on this test, stabilization or improvement from baseline in the treated eyes was observed in 9 of 12 patients (75%). For the patients with RHO mutations, 6 (86%) showed stabilization or improvement from baseline in the treated eyes in MLMT score. Three of the patients with RHO mutations achieved a 3 lux luminance level improvement from baseline in the treated eyes.

OCU400 was administered via subretinal injection to 1 eye. The trial has treated 18 adult patients with RP related to mutations in the RHO and NR2E3 genes so far, and also includes patients with LCA related to mutations in the CEP290 gene, and pediatric patients with either RP or LCA related to mutations in these genes. Patients were treated at low, medium, and high dose levels corresponding to 1.66x10¹⁰ vg/mL, 3.33x10¹⁰ vg/mL, and 1.66x10¹¹ vg/mL respectively. In terms of safety, OCU400 was deemed generally safe and well-tolerated across the spectrum of disease-related mutations and dose levels included in the study. No serious adverse events (SAEs) have been reported among the patients who received the low and medium doses of OCU400, although 1 patient who received the high dose and 1 patient included in the open enrollment cohort experienced SAEs. Ocugen stated that the surgical procedure accounted for most AEs and that in the span of a few days to weeks resolution of most was reached.

“Rhodopsin mutations are very difficult to treat. That's why there's [no gene therapies] there. And this is one of the big ones causing RP, around 10,000 patients struggle with it in the US alone. So, in those patients, we showed very encouraging results 86% 6 out of 7 patients showed improvement. So that's important. Why? Because it's proving the concept of modifier genes... the gene agnostic approach. So, if it works in rhodopsin, potentially it could work in all those patients I'm talking about, around 125 genetic mutations,” Musunuri previously told CGTLive.

REFERENCES

1. Ocugen gains FDA alignment on key aspects of OCU400—Modifier gene therapy—pivotal phase 3 study design. News release. December 21, 2023. https://www.globenewswire.com/news-release/2023/12/21/2799874/0/en/Ocugen-Gains-FDA-Alignment-on-Key-Aspects-of-OCU400-Modifier-Gene-Therapy-Pivotal-Phase-3-Study-Design.html
2. Ocugen announces positive clinical study update from the phase 1/2 trial of OCU400, a modifier gene therapy product candidate, for the treatment of retinitis pigmentosa (R) and leber congenital amaurosis (LCA). News release. September 13, 2023. Accessed September 19, 2023. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-positive-clinical-study-update-phase-12-trial