OPGx-001

The therapy is tailored to deliver a functional LCA5 gene to the outer retina using an adeno-associated virus 8 vector. Credit: Sai Thaw Kyar/Shutterstock. The US Food and Drug Administration (FDA) has awarded a regenerative medicine advanced therapy (RMAT) designation to Opus Genetics’ gene therapy OPGx-LCA5 for Leber congenital amaurosis (LCA) caused by mutations in the LCA5 gene. The designation was granted based on preliminary clinical evidence from an ongoing dose-escalation, open-label Phase I/II trial, assessing the therapy’s potential efficacy and safety in individuals with severe vision loss caused by confirmed LCA5 gene mutations. Opus Genetics has received an invitation to take part in the FDA’s initial comprehensive multidisciplinary RMAT meeting, which will support the company’s development and manufacturing strategy. It is also set to join the agency’s chemistry, manufacturing and controls (CMC) development and readiness pilot (CDRP) programme, providing further guidance for expediting CMC product development under an investigational new drug application. The designation allows for closer communication with the US regulator, offering guidance on development, manufacturing and potential surrogate endpoints for accelerated approval. OPGx-LCA5 delivers a functional LCA5 gene to the outer retina using an adeno-associated virus 8 vector, targeting a form of LCA associated with biallelic mutations in the LCA5 gene. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Individuals with LCA5-associated inherited retinal disease experience early-onset severe retinal dystrophy. Research indicates a disconnect between retinal structure and visual function in this condition, suggesting a window for therapeutic gene augmentation. The ongoing Phase I/II trial of the therapy, led by Dr Tomas Aleman at the University of Pennsylvania, US, is focused on evaluating the initial efficacy and safety in subjects with inherited retinal degeneration due to LCA5 gene mutations. Opus Genetics CEO George Magrath said: “The FDA’s decision to grant RMAT designation to OPGx-LCA5 is a major milestone for the LCA5 patient community and a strong validation of our early clinical data. “We’re encouraged by the potential of OPGx-LCA5 to meaningfully impact patients living with this ultra-rare and debilitating form of inherited blindness, and we look forward to continued collaboration with the FDA to accelerate its development.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here . We may still continue to send you service-related and other non-promotional communications. For more information relating to our privacy practices, we invite you to review our privacy policy .

First pediatric patient shows encouraging early safety profile and meaningful improvement in visual function at one month A second pediatric patient was recently dosed, and the pediatric cohort is expected to complete enrollment in Q2 2025; initial data from all three patients anticipated in Q3 2025 FDA Type D meeting provided clarity on next steps for a registrational trial design to support BLA submission, with potential trial initiation in 2026 April 08, 2025 -- Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage ophthalmic biotechnology company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and to treat other ophthalmic disorders (“Opus” or the “Company”), today announced one-month clinical data from the first pediatric patient treated with its investigational gene therapy, OPGx-LCA5, in a Phase 1/2 open-label trial for LCA5-related inherited retinal disease (IRD). The new data builds upon previously reported positive results from adult patients treated in the same study. “The preliminary results observed in our pediatric patient are encouraging and are consistent with the improvements we previously observed in adults,” said Tomas Aleman, M.D., Scheie Eye Institute Perelman, the study Principal Investigator. “She noticed that objects were significantly brighter and was able to distinguish letters and navigate with an independence she had never had before, after only one-month following treatment. We’re excited to continue enrolling patients and studying improvement over longer periods of time in this important study.” George Magrath, M.D., Chief Executive Officer of Opus Genetics added “We believe these findings provided further evidence supporting the potential of OPGx-LCA5 to restore meaningful vision in patients affected by LCA5. The meeting with the FDA regarding the design of our program may lead to the start of a trial in 2026. Early intervention may be particularly beneficial in pediatric patients, given the progressive nature of this disease.” OPGx-LCA5 is currently being evaluated in a Phase 1/2 trial in adult and pediatric patients with inherited retinal degeneration due to mutations in the LCA5 gene. The trial is progressing and began enrolling a cohort of three pediatric patients in February 2025. Initial data from this pediatric cohort are expected in the third quarter of 2025. LCA5 is a rare and severe genetic disorder that leads to early-onset vision loss due to mutations in the LCA5 gene, which encodes lebercilin, a protein essential for photoreceptor function. There are no approved therapies for LCA5-related IRD to date, making gene therapy a potentially transformative approach. The first pediatric participant, aged 16 (at time of consent), received a single subretinal injection of OPGx-LCA5 and clinically meaningful improvement in vision was observed at one-month post treatment. In addition to these promising early efficacy signals, there have been no observed drug related adverse events reported to date. These data are preliminary, and we expect to be able to read out efficacy data for all three pediatric patients in the third quarter of 2025. In the ongoing Phase 1/2 trial, we have observed early clinical proof of concept in adult patients. In previously announced results for OPGx-LCA5, we observed visual improvement in all 3 of the adult patients at six months. New one-year data from the study, to be presented at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Meeting, on May 4, 2025 provide preliminary evidence that both subjective and objective signs of efficacy in these adult patients persisted for a year. An FDA meeting was held to discuss the potential regulatory path for OPGx LCA5, including the design of a potential registrational study. Opus proposed a single arm, adaptive pivotal study, to enroll as few as 19 patients, with a primary endpoint utilizing the multi-luminance orientation and mobility test (MLoMT), which is a functional vision and patient mobility test. MLoMT is a virtual-reality version of the multi-luminance mobility test (MLMT), which provided evidence to support a prior FDA approval. The company also received constructive feedback on its proposed statistical analysis plan (SAP) as well as chemistry, manufacturing, and controls (CMC). The FDA requested additional information on these topics, and Opus plans to submit further materials and continue discussions with the FDA. Opus anticipates the pivotal trial could initiate in Q1 2026. This clinical trial was designed to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-LCA5 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. It is an open-label, Phase 1/2 trial evaluating OPGx-LCA5. The trial has been enrolling both adult and pediatric patients. Dosing of the first pediatric patients began in February 2025. Efficacy endpoints include measurement of functional vision using: 1) the Multi-Luminance orientation and Mobility Test (MLoMT); 2) Full-Field Stimulus Testing (FST), which measures the retina's sensitivity to light; and 3) microperimetry, which measures point-wise sensitivity to light. For more information, visit clinicaltrials.gov (NCT05616793). The six-month results on adult patients treated with OPGx-LCA5 were presented in a Key Opinion Leader (KOL) webinar, hosted by Opus on December 11, 2024. A copy of the presentation from the webinar can be accessed here. OPGx-LCA5 is designed to address a form of Leber congenital amaurosis (LCA) due to biallelic mutations in the LCA5 gene (LCA5), which encodes the lebercilin protein. LCA5-associated inherited retinal disease is an early-onset severe inherited retinal dystrophy. Studies in patients with this mutation have reported evidence for the dissociation of retinal architecture and visual function in this disease, suggesting an opportunity for therapeutic intervention through gene augmentation. OPGx-LCA5 uses an adeno-associated virus 8 (AAV8) vector to precisely deliver a functional LCA5 gene to the outer retina. OPGx-LCA5 is currently being evaluated in a Phase 1/2 clinical trial at the University of Pennsylvania designed to evaluate its safety and preliminary efficacy in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Opus Genetics is a clinical-stage ophthalmic biopharmaceutical company developing therapies to treat patients with inherited retinal diseases (IRDs) and other treatments for ophthalmic disorders. Our pipeline includes adeno-associated virus (AAV)-based investigational gene therapies that address mutations in genes that cause different forms of bestrophinopathy, Leber congenital amaurosis (LCA) and retinitis pigmentosa. Our most advanced investigational gene therapy program is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein and is currently being evaluated in a Phase 1/2 open-label, dose-escalation trial, with encouraging early data. Our pipeline also includes BEST1 investigational gene therapy, designed to address mutations in the BEST1 gene, which is associated with retinal degeneration. The pipeline also includes Phentolamine Ophthalmic Solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist being investigated to reduce pupil size, and APX3330, a novel small-molecule inhibitor of Ref-1 being investigated to slow the progression of non-proliferative diabetic retinopathy. Phentolamine Ophthalmic Solution 0.75% is currently being evaluated in Phase 3 trials for presbyopia and dim (mesopic) light vision disturbances. We have reached agreement with the FDA under SPA for a Phase 3 trial to evaluate oral APX3330 . The content above comes from the network. if any infringement, please contact us to modify.