An FDA advisory panel recommends approval for a novel gene therapy to treat patients with Leber’s congenital amaurosis and retinitis pigmentosa. Both diseases have related mutations to the RPE65 gene.
Spark Therapeutics is the manufacturer of voretigene neparvovec (proposed trade name will be Luxturna). The drug is administered directly to the retina via a single intraocular injection.
Though the advisory panel unanimously recommends FDA approval, the FDA will not formally decide until January 2018.
Mutant Genes Make Mutant Proteins
Both Leber’s congenital amaurosis (LCA) and retinitis pigmentosa 20 (there are many genetic variants causing retinitis pigmentosa) are caused by the inherited defective RPE65 gene.
The normal RPE65 gene makes a protein responsible for rods and cones to function properly. Defective genes do not produce a normal functioning protein, hence, the normal visual cycle of the retinal cells does not function properly. Both conditions lead to progressive blindness due to this defective protein.
Gene Therapy Replaces Mutant Gene
Luxturna will be a one time injection into each eye. Luxturna will insert functional (i.e. working) copies of the defective RPE65 DNA into the retinal cells allowing the retinal cells to manufacture “normal” proteins.
The normal proteins will then restore a normal visual cycle allowing light to be converted into electrical signals that are transmitted to the brain. These electrical signals create “vision” in the brain.
As normal DNA has been inserted into the retinal cells, the procedure should not need to be repeated.
FDA Panel Advises Approval
Both LCA and Retinitis Pigmentosa 20 have no present treatment or cure.
Spark Therapeutics has been able to achieve “Priority Review” with the FDA. Priority review allows the FDA to fast-track the review process for drugs that are likely to have a great impact for the treatment of a disease.
Patients involved in the study were challenged by a maze with various amounts of lighting. Patients were to navigate their way through a dimly lit maze. The maze was changed to prevent memorization. A majority of the patients tested showed improvement after 1 year of treatment; many able to complete the maze with the lighting equivalent to a night light. Most could not read before treatment.
Vision improvements have been maintained from 2-4 years so far.
Inherited Retinal Diseases
Inherited retinal diseases are rare blinding conditions caused by one of more than 220 different genes.
Leber’s congenital amaurosis and Retinitis Pigmentosa 20 are just two such examples of IRD caused by the mutated RPE65.
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