In a historic move, the U.S. Food and Drug Administration (FDA) today approved a gene therapy initially developed by researchers at the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) for the treatment of a rare, inherited form of retinal blindness. The decision marks the nation’s first gene therapy approved for the treatment of a genetic disease, and the first in which a new, corrective gene is injected directly into a patient.

The therapy, known as LUXTURNA™ (voretigene neparvovec-ryzl), significantly improves eyesight in patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Patients with RPE65 mutations suffer from severe visual impairment at infancy or early childhood, and by mid-life become totally blind. They previously had no pharmacologic treatment options.

Spark Therapeutics, a Philadelphia biotechnology company created in 2013 by CHOP in an effort to accelerate the timeline for bringing new gene therapies to market, led the late-stage clinical development of LUXTURNA and built in West Philadelphia the first licensed manufacturing facility in the U.S. for a gene therapy treating an inherited disease. Spark was built on the foundational research conducted over a ten-year period by CHOP’s Center for Cellular and Molecular Therapeutics (CCMT). Those efforts were led by Jean Bennett, MD, PhD, the F.M. Kirby professor of Ophthalmology at the Perelman School of Medicine at the University of Pennsylvania and Penn’s Scheie Eye Institute, and Katherine A. High, MD, who directed the CCMT and now serves as Spark’s president and head of research and development. Albert M. Maguire, MD, a professor of Ophthalmology at the Perelman School of Medicine and an attending physician at CHOP, served as the principal investigator of the clinical trials which led to today’s FDA approval.

The approval is a culmination of more than 25 years of studies on congenital blindness by married-couple team Bennett and Maguire at Penn and CHOP, starting with pioneering work in mice and dogs.

“I’ve witnessed the dramatic changes in the vision of patients who would have otherwise lost their sight, and feel exhilarated that this therapy will now make a difference in the lives of more children and adults,” Bennett said. “I’m hopeful that the path we’ve made with this research, with the help of our collaborators near and far, will be useful to other groups, so that other gene therapies can be developed faster and help more people with other diseases.”

Today’s news marks the second FDA approval for a University of Pennsylvania/CHOP-developed therapy within six months. In August, the personalized cellular therapy known as Kymriah™ was approved for the treatment of advanced acute lymphoblastic leukemia in children and young adults.

There are an estimated 1,000 to 2,000 patients in the United States with RPE65 mutations. The newly approved therapy will be available at select treatment centers across the nation.

The one-time therapy corrects the deficits resulting from mutations in the gene RPE65, which is responsible for producing proteins that make light receptors work in the retina and vision possible. To restore production of those proteins, corrected versions of the RPE65 gene are delivered in a single injection, using a genetically engineered, benign adeno-associated virus to carry the genes to the retina. Within weeks, a patient’s vision can begin to improve. The FDA recommends the use of the therapy for patients ages 12 months and older.

“Today’s landmark approval is a great moment for science and the many individuals and families who live with genetic disease,” High said. “One of the hopes of the Human Genome Project had been that it would be possible to develop gene therapy to expand therapeutic options for people with genetic disease. Now that hope is a reality. We offer our sincere gratitude to the patients and their families as well as the expert investigators who continue to participate in this and other clinical development programs."

The Penn gene therapy work tightly links animal and human health, having begun in affected mice and dogs during the 1990s. In 2001, Bennett and Maguire and Penn colleagues Greg Acland, Tomas Aleman, Samuel Jacobson, and Artur Cideciyan reported they had successfully restored the sight of three blind dogs with a canine form of LCA, in collaboration with Cornell University’s Gus Aguirre (now a professor of Medical Genetics and Ophthalmology at the University of Pennsylvania School of Veterinary Medicine) and the University of Florida’s Bill Hauswirth. After the therapy, the dogs freely navigated through a dimly lit obstacle course, whereas before they would bump into objects.
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Read the full press release here.

Editor’s Note: The University of Pennsylvania has licensed certain patent rights to Spark Therapeutics, including intellectual property that covers Luxturna, which may provide financial benefits to Penn in the future.