Optogenetic Gene Therapy MCO-010 Shows Promise in Retinitis Pigmentosa

Key Insights

• MCO-010, a novel optogenetic gene therapy, has demonstrated significant vision improvement in patients with severe retinitis pigmentosa in a Phase 2b/3 trial.
• The mutation-agnostic approach of MCO-010 targets surviving retinal cells, potentially offering a broader treatment option compared to gene-specific therapies like Luxturna.
• Nanoscope Therapeutics plans to submit a Biologics License Application to the FDA in early 2025, with MCO-010 already receiving Fast Track designation.

New research presented at the American Academy of Ophthalmology (AAO) 2024 meeting reveals promising results for MCO-010, an investigational gene therapy for retinitis pigmentosa. The Phase 2b/3 trial indicates that MCO-010 can improve vision in individuals with severe vision loss from this inherited retinal disease, for which there is currently no cure.

Mutation-Agnostic Approach

MCO-010 leverages optogenetics to target retinal cells that remain viable after photoreceptor degeneration. Unlike gene-specific therapies such as Luxturna (voretigene neparvovec), which is effective only in RPE65-related retinitis pigmentosa (0.3-1% of cases), MCO-010 employs a mutation-agnostic strategy. This involves a one-time intravitreal injection delivering Multi-Characteristic Opsin (MCO) genes via a harmless virus to these surviving cells, converting them into light-sensing cells. This approach counteracts retinal damage caused by various genetic mutations, potentially broadening its applicability to other retinal degenerative diseases like macular degeneration and Stargardt disease.

Clinical Trial Results

The randomized, controlled Phase 2b/3 trial assessed MCO-010 in patients with severe vision loss, characterized as hand motion or light perception. The study randomized 27 patients into high-dose, low-dose, and sham treatment groups. Results presented by Dr. Allen C. Ho, Director of Retina Research at Wills Eye Hospital and Chief Medical Advisor at Nanoscope Therapeutics, demonstrated statistically significant improvements in visual acuity at weeks 52 and 76 in the treatment groups compared to the sham group. Notably, 40% to 50% of treated patients gained at least three lines of vision on a standard eye chart, with some improving from light perception to 20/400 or better.

Expert Commentary

"We are finally on the brink of an impactful therapy for people with severe vision loss," said Dr. Ho. "These findings finally deliver hope to patients and ophthalmologists that something is close to being able to help them."

Regulatory Pathway and Future Directions

Nanoscope Therapeutics is preparing to submit a Biologics License Application (BLA) to the FDA in early 2025. The FDA has already granted Fast Track designation to MCO-010. Furthermore, Nanoscope is collaborating with the FDA on a Phase 3 trial design to evaluate MCO-010 in Stargardt macular degeneration, with trial start-up activities underway.