Ocugen’s Modifier Gene Therapy Shows Promise in Optical Diseases
By Mark Terry
April 17, 2023
Malvern, Pa.-based Ocugen recently announced positive preliminary safety and efficacy data from the Phase I/II trial of its modifier gene therapy product candidate, OCU400. The therapy is being evaluated for the treatment of retinitis pigmentosa (RP) and Leber Congenital Amaurosis (LCA).
Shankar Musunuri, PhD, MBA, company Chairman, CEO and Co-founder, said in a conference call, “It is gratifying to see these positive preliminary results … which support the potential to transform the lives of these patients.”
The announcement included the first two cohorts from the trial for RP associated with NR2E3 and Rhodopsin (RHO) mutations and LCA with mutations in the CEP290 gene.
RP is a group of rare eye diseases affecting the retina. The disease causes the cells in the retina to break down slowly over time, leading to vision loss and potential blindness. Similarly, LCA is a rare inherited eye disease that first appears at birth or in the first few months of life.
Ocugen differentiates its technology platform from more traditional gene therapies. They refer to their platform as “modifier gene therapies” and Musunuri said, “Unlike single gene replacement therapies that target a single gene mutation, our modifier gene therapy platform … represents a novel approach” that can treat genetic diseases “caused by imbalances in gene networks.”
Modifier genes increase or decrease the severity of the symptoms or phenotype of a disease, but don’t necessarily cure the disease itself. A number of diseases have been studied for the direct impact of genetic modifiers, including cystic fibrosis, epileptic encephalopathy, spinal muscular atrophy, and retinal degeneration. All demonstrate significantly variable phenotypes with changes in the modifier gene variants.
The platform is based on the use of nuclear hormone receptors (NHR), master gene regulators that the company believes can restore homeostasis. It has the potential to address multiple retinal diseases caused by mutations in multiple genes with one product and complex diseases caused by imbalances in multiple gene networks. The programs in the modifier gene therapy include OCU400 for RP and LCA, OCU410 for dry age-related macular degeneration (AMD) and OCU410ST for Stargardt disease.
Wet AMD is a serious form of late AMD, which occurs when a protein called vascular endothelial growth factor (VEGF) produces abnormal blood vessel growth in the back of the eye. Stargardt disease is a rare genetic eye disease caused by fatty material build-up in the macula.
Huma Qamar, MD, MPH, Ocugen’s Head of Clinical Development and Medical Affairs, in the conference call said that the company expects to file Investigational New Drug (IND) applications this quarter with the FDA for OCU410 for dry AMD and OCU410ST for Stargardt disease, adding that the company lets its “passion, dedication, commitment and compassion lead us.”
In Cohort 1 and 2 of the study, seven patients with severe vision loss due to RP associated with RHO and NR2E3 gene mutations were given a unilateral subretinal injection of one of two potential doses of OCU400. In the preliminary data analysis, the company evaluated data from three patients in Cohort 1 at nine months, and four patients from Cohort 1 at six months. The data demonstrated a favorable safety profile with visual improvements as measured by multi-luminance mobility testing (MLMT) and best-corrected visual acuity assessment (BCVA).
In the presentation, Qamar indicated the key efficacy outcomes from the seven patients showed “100% of treated eyes showed a stable or improved MLMT score trend,” and 71.4% receiving OCU400 demonstrated a 1 or more Lux level improvement in MLMT compared to 28.6% of untreated eyes. In addition, 66.7% of treated eyes in Cohort 1 with 9-month follow-up showed a 2 or more Lux level improvement in MLMT score compared to 0% of the untreated eyes, and 42.9% of treated eyes demonstrated 8-11 letters of improvement in BCVA score compared to 0% of the untreated eyes.
Speaking during the conference call, David Birch, PhD, Scientific Director, Retina Foundation of the Southwest, and principal investigator of the study, said, “I’m happy to report on behalf of our patients. I must say they are extremely motivated, and we’ve had absolutely no loss to follow-up visits.”
Birch added that the efficacy data presented “fits with the reports we’re getting back from the patients…. Above all, they are motivated to retain the vision they already have. And any improvement, which we’re seeing in the data, is a bonus.”
Ocugen is partnered on OCU400 with CanSinoBIO. CanSinoBIO provided all CMC development and clinical supplies for the trial.
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Mark Terry is a freelance writer, editor, novelist and ghostwriter. He holds a degree in microbiology & public health and spent 18 years in infectious disease research and clinical and research genetics prior to his transition to a writing career. His areas of expertise include biotechnology, pharma, clinical diagnostics, and medical practice management. He has written literally thousands of articles, as well as market research reports, white papers, more than 20 books, and many other written materials. He currently lives in Michigan with his family.
