LAUSR

AN EMERGING, vision-restoring gene therapy for a devastating retinal disease is poised for Food and Drug Administration (FDA) approval. If it gets the regulatory nod, it will be the first gene therapy to receive FDA approval for the eye or an inherited condition. The story of this groundbreaking treatment began with discovery of the gene RPE65 nearly 25 years ago at the National Eye Institute, and continued when the Foundation Fighting Blindness (FFB), the world’s leading private funding source for inherited retinal disease (IRD) research, invested $10 million in studies that linked mutations in RPE65 to blindness, and advanced an RPE65 gene therapy into clinical trials. On October 12, 2017, the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee unanimously recommended marketing approval for the investigational treatment, voretigene neparvovec (LUXTURNA), for people with vision loss from biallelic mutations in RPE65. Defects in the gene lead to certain forms of Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Affecting 1,000–2,000 people in the United States, these conditions cause devastating vision loss in childhood, including night blindness and loss of visual acuity and color perception. Eventually, nearly all patients with biallelic RPE65 mutations go completely blind. During the Advisory Committee’s hearing, representatives from Spark Therapeutics, the therapy’s commercial developer, reviewed impressive Phase 3 clinical trial results for 32 participants, some as young as 4 years of age. The company reported clinically meaningful and statistically significant vision improvements in participants’ functional vision, light sensitivity, and visual function. Results were durable for up to 3 years—the longest reported patient follow-up. The safety profile was consistent with vitrectomy and subretinal injections, which are frequently performed for the treatment of other retinal conditions. Most compelling was testimony from patients for whom the treatment was life changing (Fig. 1). After a single subretinal injection to each eye, many reported putting away their navigational canes, seeing facial expressions for the first time, enjoying a world of vibrant color, and even observing stars in the night sky. ‘‘I didn’t realize stars were little dots that twinkled,’’ said Misty Lovelace, a young woman at the hearing who received the RPE65 gene therapy in 2012. She also told the Committee that she was able to see her mother’s face clearly for the first time shortly after receiving the treatment. For the impassioned group of families who founded FFB in 1971, this was a moment they had been waiting for. But little did they know it would take more than 46 years to reach it. While it was clear in the early 1970s that virtually no research was underway to even understand how these retinal conditions occur, no one, not even the top retinal experts, had any idea how complex and diverse the diseases actually were. No one knew the formidable challenge that lay ahead. But at no point did anyone ever think of ever giving up the fight to overcome them. Through its persistent and tenacious family of