All 16 members of the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee voted to recommend Spark Therapeutic’s Luxturna (voretigene neparvovec) for regulatory approval at a landmark hearing on October 12.
If approved, the single-dose treatment for Leber congenital amaurosis (LCA) would become the first gene therapy for inherited conditions—and the second gene therapy ever, after Novartis’ CAR-T cell therapy—sold in the United States.
The FDA typically follows the committee’s counsel, and has until January 12, 2018 to approve the drug.
“It’s an exciting day for gene therapy and, in particular, ocular gene therapy,” says Stephen Yoo, MD, chief medical officer for REGENXBIO, a firm that is developing gene therapies for retinal, metabolic and neurodegenerative conditions.
The vote validates gene therapy as a viable treatment, Dr. Yoo says, adding that the drug’s movement through the regulatory pipeline also clears a path for other gene therapies to traverse in the future.
A rare and debilitating condition, LCA affects roughly 3 in every 100,000 infants and can arise from genetic mutations in more than a dozen genes. Luxturna targets and restores expression of one of these genes, called RPE65, which causes up to 16% of LCA cases. According to Spark, the therapy could benefit an estimated 6,000 people globally.
“The mutation is defined; the defect is understood,” says Yoo, who recently initiated early-stage clinical trials for a subretinal gene therapy for wet AMD using a proprietary AAV8 vector. “In the case of Luxturna, the AAV2 vector was a great choice for targeting RPE65 mutations, and they were able to see a rapid response.”
The committee’s approval comes on the heels of promising results from a phase 3 trial, in which 18 of 20 participants experienced significant gains in visual field, light perception and contrast sensitivity after a single injection of Luxturna.
While the treatment did not completely restore sight, the gains appear to stick: Improvements persisted throughout the 1-year follow-up period with no safety concerns. Spark claims the effects may last for at least 3 years, though the company has yet to determine long-term safety and efficacy in humans. Another unknown is the drug’s price tag—Spark has not yet announced how much Luxturna will cost.
Luxturna’s race to market has captured the interest of industry analysts and the public alike. One of the trial participants, Molly Troxel, an Omaha teenager declared legally blind as a child, appeared in a PBS documentary, The Gene Doctors.