Opus Genetics' OPGx-LCA5 Gene Therapy Receives FDA RMAT Designation

Opus Genetics, a biotechnology company specializing in ophthalmic treatments, has announced a significant development in its efforts to combat Leber Congenital Amaurosis (LCA), a rare inherited retinal disorder. The U.S. Food and Drug Administration (FDA) has bestowed the Regenerative Medicine Advanced Therapy (RMAT) designation on Opus's investigational gene therapy, OPGx-LCA5. This recognition underscores the promise of OPGx-LCA5, which is currently being tested in a Phase 1/2 clinical trial.

The RMAT status was granted based on early findings from ongoing research by Opus, which is investigating the safety and potential benefits of OPGx-LCA5 in patients suffering from significant vision impairment due to mutations in the LCA5 gene. The FDA's decision highlights both the robustness of the initial data and the substantial need for effective treatments within this patient group.

Dr. George Magrath, the CEO of Opus Genetics, expressed the significance of the RMAT designation, viewing it as a pivotal achievement for the LCA5 patient community and a validation of Opus's early research efforts. He emphasized the potential of OPGx-LCA5 to provide substantial benefits to those affected by this rare and debilitating form of inherited blindness. Additionally, he expressed anticipation for ongoing collaboration with the FDA to expedite the development of the therapy.

Alongside the RMAT designation, Opus has received an invitation to participate in the FDA’s Initial Comprehensive Multidisciplinary RMAT Meeting. This involvement aims to bolster Opus’s development and manufacturing strategies. Opus has also been invited to join the FDA’s Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program, which offers further guidance to accelerate the CMC development of investigational products.

The RMAT designation program is designed to facilitate the expedited development and evaluation of regenerative medicine treatments that show potential for addressing serious or life-threatening conditions based on preliminary clinical evidence. This designation allows sponsors to engage in early discussions with the FDA, obtain guidance on efficient development and manufacturing processes, and explore surrogate endpoints that may support accelerated approval.

OPGx-LCA5 targets a type of Leber congenital amaurosis caused by biallelic mutations in the LCA5 gene, responsible for encoding the lebercilin protein. LCA5-associated retinal disease is characterized by early-onset severe retinal dystrophy. Research involving patients with these mutations has indicated a dissociation between retinal structure and visual function, suggesting potential for therapeutic intervention through gene therapy. OPGx-LCA5 employs an adeno-associated virus 8 (AAV8) vector to deliver a functional LCA5 gene to the outer retina. The therapy is currently under evaluation in a Phase 1/2 clinical trial, led by Dr. Tomas Aleman at the University of Pennsylvania, to assess its safety and preliminary efficacy in patients with inherited retinal degeneration due to LCA5 mutations.

Opus Genetics is dedicated to developing therapies for inherited retinal diseases and other ophthalmic disorders. Its pipeline includes adeno-associated virus-based gene therapies targeting mutations that cause various retinal conditions, including bestrophinopathy, Leber congenital amaurosis, and retinitis pigmentosa. Opus’s most advanced program, targeting the LCA5 gene, has received RMAT designation, with encouraging preliminary data. The company is also developing other therapies, such as a gene therapy for mutations in the BEST1 gene and a novel small-molecule inhibitor, APX3330, to address diabetic retinopathy. APX3330 is undergoing Phase 3 trials for presbyopia and dim light vision disturbances, with the FDA agreeing to a Phase 3 trial to evaluate its efficacy for diabetic retinopathy.