Groundbreaking Gene Therapy Approved for Inherited Retinal Blindness

More than a decade of studies led by researchers at Children’s Hospital of Philadelphia and the University of Pennsylvania culminated this week with the U.S. Food and Drug Administration’s approval of an innovative one-time gene therapy product indicated for the treatment of patients with a rare, inherited form of retinal blindness.

Spark Therapeutics, a Philadelphia biotechnology company created in 2013 by CHOP to accelerate the timeline for bringing new gene therapies to market, led the late-stage clinical development of the therapy, known as LUXTURNA™. Spark was built on the foundational research conducted at CHOP’s Raymond G. Perelman Center for Cellular and Molecular Therapeutics under the direction of then-CHOP-researcher Katherine High, MD, a gene therapy pioneer who is now Spark’s president and head of research and development.

The initial research also was spearheaded by Jean Bennett, MD, PhD, F.M. Kirby professor of Ophthalmology at the Perelman School of Medicine at the University of Pennsylvania’s Scheie Eye Institute, and Albert Maguire, MD, a professor of Ophthalmology at Penn Medicine and an attending physician at CHOP, who served as a principal investigator of the therapy’s clinical trials. The landmark approval is a result of the dedication and perseverance of the research team and the commitment of the patients and families who participated in the clinical studies.

“The FDA’s approval of LUXTURNA highlights the vital role of pediatric research in developing breakthrough cures,” stated Bryan Wolf, MD, PhD, Executive Vice President and Chief Scientific Officer of CHOP Research Institute. “Spanning the course of 10 years, the research conducted at CHOP’s Center for Cellular and Molecular Therapeutics laid the groundwork for this revolutionary gene therapy.”

The FDA decision marks the nation’s first gene therapy approved for the treatment of a genetic disease. It is indicated for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. An estimated 1,000 to 2,000 patients in the U.S. with RPE65 mutations experience visual impairment at infancy or early childhood and become totally blind by mid-life. The therapy delivers corrected versions of the RPE65 gene in a single injection using a genetically engineered, benign adeno-associated virus to carry the genes to the retina.

Results from a pivotal phase 3 trial of 29 patients reported in 2015 showed the therapy significantly improved their ability to navigate an obstacle course designed to mimic daily activities in low light. The therapy dramatically restored most patients’ ability to see, increased their sensitivity to light, and improved their side vision. The gene therapy’s safety profile includes possible side effects such as cataracts, changes in intraocular pressure, changes in macular structure, intraocular infection in one patient, and a reduction in visual acuity in one patient.

It is anticipated that the gene therapy will be administered at selected treatment centers in the U.S. by leading retinal surgeons who will receive surgical training provided by Spark on the administration procedure. So far, 41 patients have been treated with the therapy at CHOP and the University of Iowa.

“The approval of the gene therapy approach for [Leber congenital amaurosis] opens up the door to develop therapies that target other mutations behind hereditary blindness and retinal diseases, and emphasizes the importance of genetic testing so that people living with inherited diseases can potentially benefit from gene treatments as they emerge,” Dr. Maguire stated in a press release. “It also serves as a stepping stone to more prevalent diseases.”

Read more in the CHOP and Penn press releases.