FDA approved Spark Therapeutics’ gene therapy Luxturna (voretigene neparvovec-rzyl) for treating children and adults with the rare inherited blindness disorder biallelic RPE65 mutation-associated retinal dystrophy. Approval of the one-time adeno-associated virus vector (AAV)-delivered gene therapy, which FDA Commissioner Scott Gottlieb, M.D., described in a statement as “a milestone that reinforces the potential of this breakthrough approach in treating a wide-range of challenging disease,” marks the first gene therapy approval for a genetic disease. Spark has not confirmed the cost of treatment, although some commentators are anticipating a $1 million per patient price tag. Luxturna is currently under review by the European Medicines Agency. 

FDA clearance of Luxturna marks the third approval by the agency for a gene therapy, but the first for an AAV-based treatment. In August this year, the U.S. regulator cleared Novartis’ cell-based chimeric antigen receptor T-cell (CAR-T) gene therapy Kymriah (tisagenlecleucel) for treating refractory or relapsed B-cell acute lymphoblastic leukemia. In October, Kite Pharma’s CAR-T therapy Yescarta (axicabtagene ciloleucel)  was given the FDA nod for treating refractory or relapsed diffuse large B-cell lymphoma.

Dr. Gottlieb further commented, “Today’s approval marks another first in the field of gene therapy—both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss….The culmination of decades of research has resulted in three gene therapy approvals this year for patients with serious and rare diseases. I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses.” 

Next year, the FDA aims to start rolling out a series of what it calls disease-specific guidance documents on the development of specific gene therapy products. These will “lay out modern and more efficient parameters—including new clinical measures—for the evaluation and review of gene therapy for high-priority disease where the platform is being targeted,” Dr. Gottlieb stated. “We’re at a turning point when it comes to this novel form of therapy, and, at the FDA, we’re focused on establishing the right policy framework to capitalize on this scientific opening.” 

Biallelic RPE65 mutation-associated retinal dystrophy affects 1000 to 2000 patients in the U.S. and is one of a group of retinal disorders that are caused by more than 220 different genes, and which lead to progressive visual dysfunction and potentially blindness. In the case of biallelic RPE65 mutation-associated retinal dystrophy, affected individuals have inherited mutations in both copies of the RPE65 gene, which results in reduced levels or a complete lack the RPE65 protein in retinal cells. The disorder leads to progressive loss of vision, often during childhood or adolescence, and eventual blindness. 



Administered as a subretinal injection, Luxturna uses an AAV vector to deliver a normal copy of the RPE65 gene to viable retinal cells in patients with confirmed disease. The gene therapy has been tested in two open-label Phase I studies and one open-label, controlled Phase III study, involving 41 participants aged four to 44 years at the time of treatment. 

Luxturna will be administered to patients with genetically confirmed disease, by specially trained surgeons at selected centers in the U.S. Spark anticipates that the gene therapy will be available during the first quarter of 2018. The firm will manufacture Luxturna at its facility in West Philadelphia, which it says is the first manufacturing facility in the U.S. licensed for a gene therapy to treat an inherited disease.

“During the more than 12 years of innovative research with dedicated collaborators near and far, I’ve witnessed the dramatic improvement in vision in many patients who would have otherwise lost their sight,” commented Jean Bennett, M.D. Ph.D., the F.M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania and Penn’s Scheie Eye Institute. “I believe that the success of the Luxturna clinical development program will pave the way for the development of other gene therapies that may help the millions of patients with genetic diseases who currently have limited or no treatment options.”

“This approval is a watershed milestone,” added Benjamin Yerxa, Ph.D., CEO at the Foundation Fighting Blindness (FFB), a nonprofit organization focused on research for preventing and treating blindness caused by inherited retinal diseases. “For people with an inherited retinal disease and for other patient communities, this decision may create important momentum for investigational gene therapies.”

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