How to make Cell and Gene Therapy in ophthalmology work

Part 1: CGTs in ophthalmology: The physician and patient view

Featuring:

• Vishal Singal, Partner, Head of Patient Solutions, Beghou (host)

• Marianna Weener, Retinal Physician Scientist, Broad Institute of MIT and Harvard

• Lulian Kim, patient with retinitis pigmentosa and Translator

Part 2: CGTs in ophthalmology: The outlook for gene therapy in the ophthalmology space

Featuring:

• Vishal Singal, Partner, Head of Patient Solutions, Beghou (host)

• Marianna Weener, Retinal Physician Scientist, Broad Institute of MIT and Harvard

Key takeaways:

1. So-called “founder-effect” variants change the development calculus: When many patients share the same mutation, it becomes the foundation for treatment, because one editing tool can treat the majority.
2. One example of this shared ancestry is the EYS gene mutation which affects up to 20% of retinitis pigmentosa (RP) patients in Russia and 30% in Japan.
3. Gene editing, rather than gene replacement, is the most credible current tool for treating EYS mutations, because an AAV (Adeno-associated virus) cannot deliver this construct. Safer forms of gene editing, like prime and base editing, avoid the double-strand DNA breaks that risk triggering cell death.
4. In the opinion of retinal specialists and patients with RP, regulatory endpoints for this disease need to move away from requiring measurable vision improvement. Stabilization is a meaningful outcome for patients and needs to be recognized as such by regulators, they argue.
5. Nine years on, there hasn’t been another Luxturna, the gene therapy approved for hereditary blindness. The bottleneck is not biology. Rather, approval frameworks, genomic data governance, and patient infrastructure are not keeping pace with the science.
6. In addition, investment in gene therapy tends to concentrate around familiar targets, as is the case in many areas of drug development. The ophthalmology field has enough viable targets and enough tools for biotech to take a broader view, with endpoints calibrated to this specialty rather than borrowed from oncology.