Gene-Agnostic Gene Therapy Shows Efficacy in NR2E3- and RHO- Associated Retinitis Pigmentosa

All treated eyes had stable or improved MLMT scores at 6 or 9 months of follow-up.

Ocugen’s OCU400 gene therapy has demonstrated positive preliminary data in patients with retinitis pigmentosa (RP) associated with NR2E3 and rhodopsin (RHO) mutations treated in a phase 1/2 trial (NCT05203939).

“It is very gratifying to see these positive preliminary results from our novel modifier gene therapy approach,” Shankar Musunuri, PhD, MBA, chairman, chief executive officer, and cofounder, Ocugen, said in a statement. “This is the first clinical validation of the platform where patient responses across various genetic mutations support that OCU400 has the potential to transform the lives of many patients who are struggling with debilitating blindness diseases.”

The multicenter, dose ranging, open-label study has enrolled 18 participants with RP with ages ranging from 18 to 77 years. Ten participants were enrolled in the dose escalation phase and 8 were enrolled in the expansion phase. The trial has been expanded to assess OCU400 in patients with Leber congenital amaurosis (LCA) associated with CEP290 mutations. Ocugen’s strategic partner, CanSinoBIO, provided chemistry, manufacturing, and controls development and clinical supplies for the trial.

“I was not expecting such substantial improvements in visual function among the trial participants I have been working with because of the advanced stage of their retinal disease,” principal investigator David Birch, PhD, scientific director, Retina Foundation of the Southwest, added. “I am very pleased by the outcomes I have seen in my own clinic and am hopeful that OCU400 could provide a therapeutic solution for RP patients who are not only facing loss of vision, but also challenged with the psychological burden of losing their independence.”

READ MORE: LCA1 Gene Therapy ATSN-101 Shows Phase 1/2 Promise at Highest Dose Assessed

The updated data are from 7 participants with severe vision impairment due to RP associated with NR2E3 and RHO mutations who received a subretinal injection of either low dose (1.66 x 1010 vg/mL) or medium dose (3.33 x 1010 vg/mL) OCU400 in 1 eye. Three patients had follow-up of 9 months and 4 had follow-up of 6 months.

Investigators found that all treated eyes had stable or improved multi-luminance mobility testing (MLMT) scores. Specifically, 5 of 7 treated eyes (71.4%) had at least a 1 Lux level improvement in MLMT score compared to 28.6% of untreated eyes and 2 of 3 (66.7%) treated eyes in cohort 1 with 9 months of follow-up had at least a 2 Lux level improvement in MLMT score compared to 0% of the untreated eyes. Best corrected visual acuity (BCVA) was also assessed and 3 of 7 (42.9%) of treated eyes had 8 to 11 letters of improvement compared to none of the untreated eyes.

“The early results from patients treated in the Phase 1/2 clinical trial are encouraging and support the paradigm-changing potential of modifier gene therapy technology to address unmet medical needs for patients with RP and LCA,” Arun Upadhyay, PhD, chief scientific officer and head of research, development and medical, Ocugen, added. “With this favorable safety profile and positive trend in efficacy signals, we are very eager to see longer-term data, and to potentially initiate Phase 3 trials in the US and EU.”

OCU400 is a gene-agnostic modifier gene therapy designed to deliver the NR2E3 gene that regulates physiological functions within the retina including photoreceptor development and maintenance. The therapy is intended to reset affect gene networks in the retina and reestablish homeostasis.

Ocugen announces positive preliminary safety and efficacy results from the phase 1/2 trial of OCU400, a modifier gene therapy product candidate, for the treatment of retinitis pigmentosa and Leber congenital amaurosis. News release. Ocugen. April 14, 2023.
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