Ocugen’s Retinitis Pigmentosa Gene Therapy OCU400 Sustains or Improves Visual Function in 2-Year Follow-Up Data
Among 9 patients treated in the study who were evaluable at 2 years posttreatment, all 9 showed improved or preserved visual function in comparison to their untreated fellow eyes.
Arun Upadhyay, PhD
Ocugen’s OCU400, an investigational gene therapy product based on the company’s Modifier Gene Therapy Platform, has demonstrated the ability to sustain or improve visual function in comparison to untreated eyes in patients treated in a phase 1/2 clinical trial (NCT05203939) in retinitis pigmentosa (RP), according to newly announced 2-year follow-up data.1
Among 9 patients treated in the study who were evaluable at 1 year and 2 years posttreatment, all 9 (100%) showed improved or preserved visual function in comparison to their untreated fellow eyes at both time points. Furthermore, all 9 evaluable patients (100%) showed improvement or stabilization on mobility testing at 1 year posttreatment; mobility testing was not carried out again after this time point. Notably, at 2 years posttreatment, the improvements recorded in visual function compared to untreated fellow eyes were determined to be statistically significant (P = .01) without regard to the underlying mutation causing the patient’s RP.
RP is associated with over 100 genes.2 Because of the wide range of genes implicated in the condition, it is unlikely to be feasible for gene therapy approaches targeted at each specific gene to be developed and commercialized in a reasonable amount of time. In order to work around this issue, Ocugen developed its Modifier Gene Therapy Platform, which is intended to allow for a gene-agnostic approach to treating IRDs.
OCU400 is an adeno-associated virus gene therapy delivering a nuclear hormone receptor gene called NR2E3.1 The therapy is designed to reset the dysfunctional gene network in patients with RP, regardless of their specific mutation, and reestablish a healthy cellular homeostasis via NR2E3’s regulation of photoreceptor development and maintenance, metabolism, phototransduction, inflammation, cell survival, and other physiological functions.
"It is truly remarkable to see the significant improvements in visual acuity in patients treated with OCU400 sustained at 2 years,” Syed M. Shah, MD, FACS, vice chair for research and digital medicine, and the director of retina service at Gundersen Health System, La Crosse, Wisconsin, said in a statement.1 “The broad spectrum of genes and mutations causing RP presents a unique challenge in developing treatments for this unmet need. This is where the promise of mutation-agnostic therapies becomes particularly compelling. OCU400’s demonstrated effectiveness across multiple mutations not only offers hope to RP patients but also opens new possibilities for treating other retinal diseases."
In terms of safety, there were no serious adverse events deemed related to OCU400 reported in the trial. The long-term safety and tolerability profile was characterized as “favorable” by Ocugen based on the results.
“Establishing the long-term safety and efficacy of OCU400 demonstrates the durability of this novel gene therapy,” Huma Qamar, MD, MPH, the chief medical officer at Ocugen, added to the statement.1 “These 2 year low light visual acuity (LLVA) findings, which are the most sensitive measure of visual function, are consistent with the results observed at one year.”
In addition to the phase 1/2 trial, OCU400 is also being evaluated in the phase 3 liMeliGhT clinical trial (NCT06388200), which dosed its first patient in June 2024.2 The phase 3 trial will last 1 year and include 150 participants, at least 8 years of age. The trial includes an arm for patients with RHO gene mutationsand a gene agnostic arm; each arm will include approximately half of the participants in the study. Furthermore, each arm will randomly assign patients in a 2:1 fashion to receive either 2.5x1010 vg/eye of OCU400 or control. Shortly after the dosing of the first patient in liMeliGhT was announced, CGTLive® interviewed Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen, to learn more about its design.
“The primary efficacy end point for this particular phase 3 study is assessment of patient mobility through a maze-like path under different light conditions, or in other words, what we call under different lux level conditions,” Upadhyay told CGTLive. “We named this test LDNA, Luminance Dependent Navigation Assessment. Basically what we are doing on this test is that the way we define the treatment benefit is someone who shows improvement of 2 lux levels or more from baseline after 12 months of treatment. How did we come to this number? It is based on our phase 1/2 study, where over 60% of the intent to treat patient population saw a vision improvement of 2 lux levels or more. Based on this phase 1/2 responder outcome, we powered our phase 3 study more than 95%, with the assumption of 50% patient responders in our phase study 3 meeting a 2 lux or more level of improvement as a responder criteria.”
