Spark Therapeutics Inc.'s experimental gene therapy Luxturna on Oct. 12 won the unanimous backing of a U.S. Food and Drug Administration advisory panel, making the drug's chances for U.S. approval more favorable.
The FDA's Cellular, Tissue and Gene Therapies Advisory Committee voted 16-0 that Spark's clinical trial data demonstrated that Luxturna's benefits outweighed its risks in treating vision loss due to confirmed biallelic RPE65 mutation-associated retinal dystrophy.
The rare progressive genetic eye disease causes significant visual impairment, eventually resulting in near total blindness.
Luxturna works by supplying a functional copy of the RPE65 gene within the retinal pigment epithelium cells, allowing for restoration of the visual cycle, according to Spark.
If approved, it would be the first drug available in the U.S. to treat the eye disease and the first gene therapy for retinal use.
The FDA is expected to act on Luxturna by Jan. 12, 2018. The agency is not required to take the advice of its expert advisory panels, but generally does so.
There is currently only one gene therapy approved for the U.S. market — Novartis AG's Kymriah, a chimeric antigen receptor T-cell, or CAR-T, therapy, which gained the FDA's nod on Aug. 30 to treat pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Gilead Sciences Inc. is awaiting word by Nov. 29 from the FDA on its own similar CAR-T gene therapy, axicabtagene ciloleucel, which the company obtained through its $11.9 billion acquisition of Kite Pharma Inc.
Some critics, however, have argued that CAR-T drugs are not gene therapies and that Luxturna should be considered the first, if approved.
But the FDA has disputed that notion, arguing there are a variety of gene therapies.
"CAR-T cells are a form of gene therapy, as the patient's T cells are genetically modified to enable them to recognize and destroy cancer cells," an FDA spokeswoman explained.
Given some of the criticism Novartis has faced with its $475,000 list price for Kymriah, Luxturna's cost, which Spark has not disclosed, may be a concern for payers.
RBC Capital Markets analyst Matthew Eckler has predicted Spark would set the list price for Luxturna at $450,000 per eye. Based on that amount, he estimated the company could bank as much as $550 million in worldwide sales at its peak.
While biallelic RPE65 mutation-associated retinal dystrophy is "exactly the type of disease we hope gene therapy would someday treat, Wilson Bryan, director the FDA's Office of Tissues and Advanced Therapies, cautioned that "our enthusiasm in the field of gene therapy must be balanced by careful consideration of the data."
Even though Spark's gene therapy demonstrated improvement in vision in patients who received a one-time subretinal injection in the clinical trial and the benefit was maintained throughout the one-year follow-up period, it is unclear if that effect decays over time, regulators said, noting the lack of long-term data.
In Spark's study, a two-light level or more improvement in multi-luminance mobility testing occurred at one year in 11 of the 21 patients, or 52%, using both-treated eyes and 15 of the 21 participants, or 71%, using the first-treated eye.
The FDA's Bryan noted Luxturna's primary evidence of effectiveness was based largely on a novel endpoint — multi-luminance mobility testing, which was designed to assess the ability of a patient to navigate the course accurately and at a reasonable pace at different light levels.
"We are uncertain whether the product's activity, as demonstrated by an effect on this novel endpoint, represents a true improvement on lives of patients," Bryan told the committee.
While regulators raised concerns about Luxturna's potential side effects, including endophthalmitis, macular holes, foveal dehiscence, retinal hemorrhage, retinal tears, elevated intraocular pressure and cataract development — events that may have long-term consequences, especially if they were left untreated — the panelists said they felt confident those could be managed.
Spark tested Luxturna in patients ages 4 to 44 years but would like to market the drug in patients as young as 3 years.
Many of FDA's panelists recommended the agency not impose a minimum age requirement for Luxturna use, noting the human eye usually is completely formed by the time a child is 3 years old and children younger than that age often undergo needed eye surgery.