Rare Disease Report

FDA Advisory Board Votes 16-0 in Favor of Gene Therapy

OCTOBER 12, 2017
RDR Staff
Today, the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue and Gene Therapies Advisory Committee met to review the data presented by Spark Therapeutics as the company attempts to obtain approval of Luxturna (voretigene neparvovec). The one-time gene therapy is intended to treat vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease.

The Committee voted 16-0 in favor of the drug.

Patients with RPE65-mediated inherited retinal dystrophy frequently suffer from night blindness (nyctalopia) as a result of decreased light sensitivity during childhood or early adulthood, as well as involuntary back-and-forth eye movements (nystagmus). As the disease progresses, total blindness can occur.

Luxturna, if approved, would be the second gene therapy approved in the United States. Kymriah was approved for the treatment of acute lymphoblastic leukemia (ALL) in August.

The Advisory Committee looked at the data for Luxturna, including Phase 3 study published in Lancet showing the gene therapy to be effective. In that study, 20 patients were given gene therapy and compared to 9 controls. At 1 year, mean bilateral multi-luminance mobility testing (MLMT) change score was 1.8 (standard deviation = 1.1) light levels in the gene therapy group versus 0.2 (standard deviation = 1.0) in the control group (P = .0013). 

The reports provided to the Advisory Committee by the FDA and Spark Therapeutics were both optimistic about the drug and its efficacy. Of concern to the FDA are whether the outcome measure (MLMT) is a relevant outcome measure and at what stage of disease severity should the gene therapy be used since the subretinal injection procedure does raise safety concerns.

The Committee said: “There were discussions about various ways to present the data on MLMT, in general agreement that this was informative about the clinical meaningfulness and potential quality of life, related to patients that were involved in the study, and potentially also relevant for future clinical use. In summary, in terms of age, at least it has been recommended as it relates to the severity of baseline, that the benefits outweigh the risks of surgical intervention.

The FDA also asked the Advisory Committee on their opinion of the duration of the treatment. Theoretically, the gene therapy should only be needed to be applied once but data is only available for 1 year.

The Committee said: “The duration and the dose of prednisone given to these patients seems unlikely in themselves to lead to significant morbiditiy considering the seriousness of the disease. The prospective natural history data for RPE65 retinal degenerations are kind of hard to come by, and visual acuity taken is one measurement that can vary significantly even with the relatively narrow age range.”

“The nice thing about this is that everything fell together,” it was said as the meeting concluded. “It was not that you had one endpoint. It seems like everything makes sense in the same way, and that is reassuring. Everything held that. They did the right analyses, and they were strong analyses. The data was presented in a good way, and everything fell together in a nice way. It is very strong data.”

The FDA will make is final decision on whether to approve Luxturna by its Prescription Drug User Fee Act (PDUFA) date of January 12, 2018.

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