FDA Approves Novel Gene Therapy for Rare Form of Vision Loss

Marcia Frellick

December 19, 2017

The US Food and Drug Administration (FDA) today approved a new gene therapy to treat a rare form of inherited vision loss that can lead to blindness.

Voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics) is targeted for adults and children with confirmed biallelic RPE65 mutation–associated retinal dystrophy, a disease that affects between 1000 and 2000 people each year in the United States.

The treatment, which is delivered surgically via subretinal injection, is the first gene therapy approved in the United States that targets a disease caused by mutations in a specific gene.

An advisory committee to the FDA unanimously recommended this therapy in October.

The RPE65 gene normally provides instructions for making an enzyme that is essential for normal vision. When there are mutations, that process is blocked, resulting in impaired vision. Luxturna works by sending a normal copy of the RPE65 gene directly to retinal cells, which can then produce the normal protein to restore vision.

The most common adverse reactions are conjunctival hyperemia, cataract, increased intraocular pressure, and retinal tear, according to the FDA press release.

The therapy, however, could come at a hefty price.

The Washington Post reported today that analysts speculate that treatments could cost as much as $1 million for both eyes.

Asked to comment about this in a press briefing on the approval today, FDA Commissioner Scott Gottlieb, MD, referred reporters to the company.

"Fundamental" Advance

But the scientific advance this latest approval represents is clear.

Dr Gottlieb told reporters, "We're at the inflection point in medicine and health, witnessing now the advent of new technology platforms that have the potential to improve health and cure disease in fundamentally novel ways."

Keeping up with the advances also provides challenges to the usual methods of product regulation, he said, to get novel products to consumers with the same gold-standard expectations for efficacy and safety.

"The approval today of the first directly administered gene therapy is especially notable, not only for what the new treatment does and how it works by engineering a virus as a vehicle to deliver the gene directly to its target inside the body, but also for how we've expanded the use of gene therapy beyond the treatment of cancer for the treatment of vision loss for children and adults," Dr Gottlieb said.

Two other gene therapies approved this year are known as chimeric antigen receptor (CAR) T-cell therapies and involve reprogramming a patient's own cells to enable them to recognize and destroy cancer cells.

Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, told reporters that Luxturna adds a different discovery.

This one represents a more traditional form of gene therapy. Viruses are modified so they don't cause disease and are used to carry therapeutic genes to human cells, in this case retinal cells.

"In contrast to the previous approvals, which we are essentially calling personalized cell–based gene therapy products, today's approval is for a gene therapy product that can be given directly to an individual to treat a disease," Dr Marks said.

He said the FDA is looking to maximize its accelerated programs to move revolutionary products ahead.

In this case, the FDA worked with the manufacturer to arrive at an innovative clinical endpoint to evaluate Luxturna that would demonstrate a meaningful effect for patients. The pivotal evidence for Luxturna was based on a phase 3 study with 31 participants, and it measured change in 1 year in a participant's ability to navigate an obstacle course at various light levels. Those in the Luxturna group showed significant improvements compared with the control group.

Many More in the Pipeline

Approval for Luxturna came well ahead of the application's goal date, Dr Marks said. And the same pathway will be open to others.

"Next year, we'll begin issuing a suite of disease-specific guidance documents on the development of specific gene therapy products," Dr Gottlieb added.

The policies will guide evaluation of gene therapies for high-priority diseases and will address high-interest areas, such as more common single-gene disorders, he said.

"We intend to provide innovators with clear advice on safe and effective development pathways including potential accelerated approval endpoints," Dr Gottlieb said.

Other treatments are already poised to make breakthroughs in the next few years, he said.

"There are more than 600 active investigational new drug applications related to gene therapy products," he said. Though he can't confirm the numbers, he said, "researchers at the Massachusetts institute of Technology estimate that about 40 gene therapies might win approval by 2022 from a current pipeline of 932 development candidates."

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