FDA Approves Spark Therapeutics' Voretigene Neparvovec-rzyl

The US Food and Drug Administration (FDA) has approved Spark Therapeutics’ voretigene neparvovec-rzyl (Luxturna), a new gene therapy treating children and adult patients with an inherited form of vision loss which may result in blindness.

Luxturna is the first directly administered gene therapy approved in the US targeting a disease caused by mutations in a specific gene.

“I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses,” Scott Gottlieb, MD, commissioner, FDA, 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.”

The therapy is approved for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy which leads to vision loss, potentially causing complete blindness in certain individuals.

“This milestone reinforces the potential of this breakthrough approach in treating a wide range of challenging diseases,” Gottlieb added.

The therapy should be administered to patients who have viable retinal cells as determined by the treating physician.

Treatment is administered via subretinal injection by a surgeon and must occur separately in each eye on separate days with at least 6 days between surgical procedures.

Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to the therapy. The most common adverse effects from Luxturna include conjunctival hyperemia, cataract, increased intraocular pressure and retinal tear.

Through Luxturna, a normal copy of the RPE65 gene is delivered directly to retinal cells, which then produce the normal protein that converts light to an electrical signal in the retina, restoring patient’s vision loss.

It uses a naturally occurring adeno-associated virus that has been modified using recombinant DNA techniques to deliver the normal human RPE65 gene to the retinal cells.

It established its safety and efficacy in a clinical development program with 41 patients between ages 4—44 years with clinically-confirmed biallelic RPE65 mutations and sufficient viable retinal cells.

Luxturna was given priority review status by the FDA in June, accelerating the biologics license application process by 4 months.

The FDA is working with partners in research and the developmental community to extend opportunities offered by gene therapy innovation to create tailored standards for evaluating the safety and effectiveness of novel technologies.

This will in turn enable the agency’s commitment to understand the fundamental clinical risks and potential benefits presented in the various technology platforms under review.

“Today we mark an important step in this progress,” Gottlieb said. “The approval 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 to the treatment of vision loss for children and adults.”

Next year, to advance gene therapy, the FDA will begin issuing a suite of disease-specific guidance documents on the development of specific gene therapy products. These documents will be a part of a framework to guide and advance the gene therapy space, while simultaneously ensuring new products meet FDA standards.