FDA Approves Gene Therapy for Inherited Blindness

FDA Approves Gene Therapy for Inherited Blindness

The U.S. Food and Drug Administration has approved a new form of gene therapy for inherited blindness. This is the first time a directly administered gene therapy has been approved for use in the United States by the FDA. The approval has raised hopes that other forms of gene therapy, including CRISPR-Cas9, may also be approved for use in the future.

The approval is for Luxturna, a new form of gene therapy for inherited blindness developed by Philadelphia biotechnology company Spark Therapeutics. Luxturna treats a rare genetic form of retinal blindness that affects between one in 1000 and 2000 people in the US – Biallelic RPE65 mutation-associated retinal dystrophy.

With biallelic RPE65 mutation-associated retinal dystrophy there are mutations in a gene called RPE65, which is responsible for triggering the production of an enzyme essential for the survival of retinal cells. The genetic mutations result in a total lack of the enzyme, or reduced levels. Without the enzyme, or at low levels, individuals with the mutations will gradually lose their vision and may completely lose their sight.

Patients suffering from the condition have two inherited RPE65 genes, one from the mother and one from the father, and there is a genetic mutation in both copies of the gene.

In contrast to other new forms of gene therapy such as CRISPR-Cas9, Luxturna does not make permanent changes to the DNA in cells. Instead, Luxturna inserts extra copies of the RPE65 gene into the DNA and uses cells’ own machinery to help the body repair the defect.

The FDA has approved Luxturna for use in children and adults, following a successful clinical trial involving 41 patients aged between 4 and 44. In the trial, patients with confirmed biallelic RPE65 mutations had Luxturna injected directly into retinal cells. Luxturna uses a modified adeno-associated virus to deliver the human RPE65 gene, allowing cells to start producing the missing enzyme.

In Phase 3 of the clinical trial, 31 patients were studied over the course of a year and improvements in vision were monitored by their ability to navigate an obstacle course at varying light levels. Compared to the control group, the Luxturna-treated patients shows significant improvements in their vision at low light levels.

The treatment was well tolerated, with side-effects limited to conjunctival hyperemia, cataracts, increased intraocular pressure, and retinal tears.

The FDA recommends patients receiving this new gene therapy for inherited blindness should also be given oral prednisone to reduce the potential for an adverse immune response.

“Patients with biallelic RPE65 mutation-associated retinal dystrophy now have a chance for improved vision, where little hope previously existed,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). Marks also said, “The approval of Luxturna further opens the door to the potential of gene therapies.”

FDA Commissioner Scott Gottlieb, M.D., said, “Today’s approval marks another first in the field of gene therapy — both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss — and this milestone reinforces the potential of this breakthrough approach in treating a wide-range of challenging diseases.”

After three decades of research, three new gene therapies have been approved for use in the United States by the FDA in the space of a year. “We’re at a turning point when it comes to this novel form of therapy and at the FDA, we’re focused on establishing the right policy framework to capitalize on this scientific opening. Next year, we’ll begin issuing a suite of disease-specific guidance documents on the development of specific gene therapy products to lay out modern and more efficient parameters — including new clinical measures — for the evaluation and review of gene therapy for different high-priority diseases where the platform is being targeted,” said Gottlieb.

There is one caveat to the new gene therapy for inherited blindness. The cost. While the cost of the treatment has yet to be disclosed, many believe it could be in the region of $1 million. That will ultimately limit the number of patients that can have the treatment performed.

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