If the FDA follows an advisory committee’s lead, the agency will approve a gene therapy that treats a rare form of blindness by early next year. Spark Therapeutics Inc.’s Luxturna (voretigene neparvovec) would be the first gene therapy in the United States for an inherited disease and the first therapy where a corrective gene is given to a patient. It also may be the first therapy in the United States to top $1 million for a single patient.

Spark’s Biologic License Application is for treatment of patients with vision loss due to biallelic RPE65-mediated inherited retinal disease. Between 1,000 and 3,000 people in the U.S. are affected by the disease, which can result in Leber congenital amaurosis or retinitis pigmentosa. Most people with the condition eventually will go completely blind, as there is no treatment available for it. But that may change soon: Data on Luxturna were so convincing that on Oct. 12, the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee voted 16-0 recommending its approval.

According to an FDA briefing document, “The clinical development program has shown that voretigene neparvovec improves both functional vision and visual function in patients with RPE65 mutation-associated retinal dystrophy for up to 3 years, with observation ongoing, and with a safety profile consistent with this type of injection procedure.…The overall efficacy and safety results from the clinical program demonstrated that the benefit-risk balance is strongly in favor of voretigene neparvovec for the treatment of patients with vision loss due to confirmed biallelic RPE65 mutation-associated retinal dystrophy.”

Dosing is once per eye by a subretinal injection. A genetic test can identify people who have a defective RPE65 gene.

“The meeting went very, very well,” says Stephen M. Rose, Ph.D., chief research officer at the Foundation Fighting Blindness, which provided early support of the research that helped produce the therapy. Not only was the vote unanimous, but there also were no abstentions, he points out. “The committee raised some important questions,” including “how long will [the effects] last, and will patients need re-treatment?” The data presented at the meeting were based on a four-year time frame, but Rose tells AIS Health he knows of individuals who were treated more than nine years ago and are still seeing.

“What’s going to happen long term as far as what the durability is going to be we’ll have to wait and see,” he says, noting that there is a 15-year study underway.

Asked to comment on the significance of this therapy and its potential approval, Rose replies, “The bottom line is it’s highly significant.” If approved, the therapy would “provide proof of principle of a genetic therapy for inherited orphan retinal disease,” as well as have “a tremendous impact on an individual’s quality of life.”

Not Everyone Responds to Therapy

Not everyone responds to the treatment, particularly older individuals in which “more retinal degeneration has happened.” That said, Rose tells AIS Health that he knows of some older people who had an improvement in their vision. For example, he cites a 44-year-old woman who regained enough vision that she was able to walk to her kids’ elementary school in order to walk them home. But at this point, it “remains to be determined” whether there is an appropriate age group for the therapy. “As with any disease, the earlier you treat it, the better” the outcomes, he says. “Obviously if we could treat people before any degeneration started,…that would be huge.”

Potentially the biggest issue with the therapy is whether it could be administered to children under the age of three years old, says Rose. “We don’t want to cause damage.” Perhaps the situation could be addressed by an intravitreal administration of the product rather than the current subretinal one, he notes. “That’s very much a different technology.”

One aspect of the therapy that has people watching the FDA decision closely is, not surprisingly, the price of the therapy. Following the FDA approval of the first chimeric antigen receptor T cell (CAR-T) therapy, Novartis Pharmaceuticals Corp.’s Kymriah (tisagenlecleucel), that company revealed its plans to launch the one-time treatment for B-cell precursor acute lymphoblastic leukemia at a price of $475,000 (SPN 9/17, p. 4).

While Spark has said the price for Luxturna has not been determined yet, analysts are estimating it could have a $1 million price tag. Even lower estimates place it well above the $500,000 mark.

Asked about the potential pricing for the drug, Rose says that “the foundation’s position is that anybody who could benefit from this should have access…Pricing is not our bailiwick.” His group’s mission is to be able to tell anyone with an inherited retinal disease, “Don’t worry; you’re not going to lose your vision,” as opposed to “There’s nothing we can do.”

Luxturna, he hopes, will be the “opening salvo in treatments that are going to make improvements” for all of these people. There are more than 18 other gene therapy clinical trials for inherited retinal diseases ongoing, he adds.

This therapy, Rose wants health plans to know, is “life changing for those individuals who receive a benefit from this.” They go “from darkness” and perhaps being “dependent on others” to gaining “independence, mobility and a significant increase in quality of life.”

“The juice is worth the squeeze,” he maintains.

The therapy has breakthrough therapy, orphan drug and rare pediatric disease designations, as well as priority review. Its Prescription Drug User Fee Act date is Jan. 12, 2018.