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The culmination of decades of research has resulted in three gene therapies being approved by the FDA this year for patients with serious and rare diseases and FDA believes that a turning point has been reached when it comes to this novel form of therapy.
Voretigene Neparvovec-Rzyl (Luxturna) is approved for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that leads to vision loss and may cause complete blindness in certain patients.
Hereditary retinal dystrophies are a broad group of genetic retinal disorders that are associated with progressive visual dysfunction and are caused by mutations in any one of more than 220 different genes. Biallelic retinal pigment epithelium-specific 65 kDa protein RPE65 gene mutation-associated retinal dystrophy affects approximately 1,000 to 2,000 patients in the U.S. Biallelic mutation carriers have a mutation (not necessarily the same mutation) in both copies of a particular gene (a paternal and a maternal mutation). The RPE65 gene provides instructions for making an enzyme (a protein that facilitates chemical reactions) that is essential for normal vision. Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. Individuals with biallelic RPE65 mutation-associated retinal dystrophy experience progressive deterioration of vision over time. This loss of vision, often during childhood or adolescence, ultimately progresses to complete blindness.
Voretigene Neparvovec-Rzyl (Luxturna) works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore patient’s vision loss. Voretigene Neparvovec-Rzyl (Luxturna) uses a naturally occurring adeno-associated virus, which has been modified using recombinant DNA techniques, as a vehicle to deliver the normal human RPE65 gene to the retinal cells to restore vision.
Voretigene Neparvovec-Rzyl (Luxturna) should be given only to patients who have viable retinal cells as determined by the treating physician(s). Treatment with Voretigene Neparvovec-Rzyl (Luxturna) must be done separately in each eye on separate days, with at least six days between surgical procedures. It is administered via subretinal injection by a surgeon experienced in performing intraocular surgery. Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to Voretigene Neparvovec-Rzyl (Luxturna).
The safety and efficacy of Voretigene Neparvovec-Rzyl (Luxturna) were established in a clinical development program with a total of 41 patients between the ages of 4 and 44 years. All participants had confirmed biallelic RPE65 mutations. The primary evidence of efficacy of Voretigene Neparvovec-Rzyl (Luxturna) was based on a Phase 3 study with 31 participants by measuring the change from baseline to one year in a subject’s ability to navigate an obstacle course at various light levels. The group of patients that received Voretigene Neparvovec-Rzyl (Luxturna) demonstrated significant improvements in their ability to complete the obstacle course at low light levels as compared to the control group. In the light of the fact that these have been small trials only with a very limited number of participants, the manufacturer plans to conduct a post-marketing observational study involving patients treated with Voretigene Neparvovec-Rzyl (Luxturna) in order to further evaluate its long-term clinical safety.