First FDA-Approved Gene Therapy Procedure for Inherited Disease Performed

Joan Miller, MD

Today, Massachusetts Eye and Ear hospital performed the first procedure using voretigene neparvovec-rzyl (Luxturna) for patients with a form of inherited blindness since its approval by the US Food and Drug Administration (FDA).

This is the first time any FDA-approved gene therapy has been given to a patient for any inherited disease.

“Today we celebrate the decades of work by many individuals to bring gene therapy from science fiction to clinical reality for patients with inherited retinal disease,” Joan Miller, MD, chief of ophthalmology, Mass. Eye and Ear and Mass. General Hospital, and the David Glendenning Cogan Professor and chair of ophthalmology, Harvard Medical School, said in a statement. “Gene therapy will now join the list of innovative therapies used routinely at Mass. Eye and Ear to treat patients. We are thrilled at Mass. Eye and Ear to be one of the first centers to offer this life-changing therapy to patients, and proud of our long, successful history of developing translational retinal therapies.”

Luxturna, developed by Spark Therapeutics, was approved in December by the FDA for patients 12 months of age and older. Clinical trials demonstrated the improvement in visual function in children and adults with inherited retinal disease caused by mutations in the gene RPE65.

The safety and efficacy of Luxturna were established in a clinical development program with 41 patients between ages 4—44 that had confirmed biallelic RPE65 mutations.

The primary evidence was based on a phase 3 study with 31 participants that measured the change from baseline to 1 year in a subject’s ability to navigate an obstacle course at various light levels. Patients that received Luxturna demonstrated significant improvements in the ability to complete the obstacle course at low light levels versus the control group.

The most common adverse effects included conjunctival hyperemia, cataract, increased intraocular pressure and retinal tear.

The treatment involves injecting a modified virus into a patient’s eyes to correct a deficiency caused by mutations in the RPE65 gene. The gene mutations prevent the production or function of a protein needed for proper functioning of the retina that leads to vision loss and may cause complete blindness in certain patients.

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.

“The approval of Luxturna further opens the door to the potential of gene therapies,” Peter Marks, MD, PhD, director, FDA’s Center for Biologics Evaluation and Research, said in a statement regarding the December approval. “Patients with biallelic RPE65 mutation-associated retinal dystrophy now have a chance for improved vision, where little hope previously existed.”

Following the approval FDA commissioner Scott Gottlieb, MD, said he believed gene therapies like Luxturna will soon be mainstays “in treating, and maybe curing, many of our most devastating and intractable illnesses.”

While trial evidence demonstrated the success that the novel gene therapy holds for patients, the therapy’s cost came into question. On January 3, Spark Therapeutics priced its approved potential blindness healer at $850,000 for one-time operation or $425,000 per eye.

“Promoting the potential cure for a form of blindness, while also making it inaccessible to most patients by cost is repugnant,” Michael Steck, OD, said in an opinion column. “These therapies may very well cure diseases, but the means to get it will kill the patient.”

The procedure, performed by Jason Comander, MD, PhD, associate director, Inherited Retinal Disorders Services, Mass. Eye and Ear, was administered to a 13-year-old boy from NJ.

“Our hope is that our ophthalmology community can leverage Luxturna’s success to accelerate the development of similar gene therapies for the many blinding retinal diseases that still afflict our patients,” Miller added.

Mass. Eye and Ear is one of only 8 medical centers in the US certified to perform the gene therapy.