Genetic Treatment for Blinding Disease Shows Vision Improvement

Newswise — Philadelphia PA – New data published in the Journal Science Translational Medicine shows encouraging results in a worldwide clinical trial for patients diagnosed with the neuro-degenerative blinding eye disease; Leber Hereditary Optic Neuropathy (LHON.) The disease is an inherited form of vision loss estimated to affect 1 in 30,000 to 50,000 individuals. LHON most often afflicts people with rapid onset of blindness in the prime of their life - men and women in their teens or twenties. Males are about four to five times more likely than females to be affected with the condition. 

REVERSE is a randomized, double masked, sham-controlled, multi-center, phase III clinical trial that evaluated the efficacy of a single intravitreal injection of ND4 in subjects with visual loss from LHON. The gene therapy trial, which took place at seven centers worldwide including at Wills Eye Hospital in Philadelphia, involved treating patients over age 15 with LUMEVOQ® (Gensight Biologics, Paris, France) gene therapy for a mutation in the ND4 mitochondrial gene. One eye was injected with the gene and the other with a sham injection. While there was hope for improvement in the eye injected with the proper gene, the unexpected finding in the REVERSE trial was bilateral improvement in visual acuity from a unilateral injection.  

In order to explain the unexpected bilateral improvement of visual function, this paper also reports the results of a parallel non-human primate study. After unilateral injection of the gene therapy, evidence of viral vector DNA was discovered in the anterior segment, retina, and optic nerve of the contralateral uninjected eye.  This supports “a plausible mechanistic explanation for the unexpected bilateral improvement in visual function seen in LHON subjects treated with a unilateral injection of the ND4 gene therapy vector” according to the study. 

“We are pleased that we’ve seen improvement to this extent in our patients dealing with this devastating vision loss – especially those at such a young age. The data shows sustained visual improvement in both eyes over the 96-week follow up period. That underscores the importance of this research and the continuing important scientific work to bring it to market,” said Robert C. Sergott, MD, Chief of Wills Eye Neuro-Ophthalmology Service, Wills Eye Hospital. 

These results show a clinically meaningful improvement over baseline +15ETDRS letters in the average best corrected visual acuity of injected eyes of the 37 REVERSE patients 96 weeks after treatment. The patients’ other eye, which received a sham injection, experienced an average visual acuity gain over baseline of +13 letters equivalent. 

Mark L. Moster, MD, Principal Investigator of the REVERSE trial at Wills Eye, said “Most impressive to me was an average greater than 5-line improvement of visual acuity from the patients’ worst vision (nadir), which is well beyond the natural history of recovery in patients with ND4 LHON. From a standpoint of the patients’ quality of life, there were significant improvements on the well-established National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Many who entered the study legally blind were no longer legally blind at the end of the study.”

The gains were most impressive when comparing improved vision against the worst vision in patients experience throughout their condition. 81% of patients showed a clinically relevant recovery (CRR) from the worst point of vision loss in one or both eyes. 

One of those patients in the study was 27-year old Haley Hampton of Philadelphia. Ms. Hampton was diagnosed at age 22 at Wills Eye after experiencing unexplained, sudden and rapidly deteriorating vision. “All of a sudden, my vision became very blurry. It prevented me from reading, getting around, and working in my career field as a fashion stylist. I had difficulty seeing colors and many important details of close-up work,” she said. “Once enrolled in the trial and I received the injection, I noticed a visual improvement about two to three weeks later. I was reading more letters every time I had a follow up appointment with the doctors at Wills,” said Hampton. 

Julia A. Haller, MD, Wills Eye Ophthalmologist-in-Chief, retina specialist and a treating physician in the Wills Eye trial, said “How exciting and inspiring to yet again see Ophthalmology at the tip of the spear in pioneering medical innovation. This landmark study offers hope for the brave young people battling this blinding condition. Gene therapy is no longer a futuristic dream – it can and does provide help and hope in the dynamically evolving field of vision restoration.” 

“It’s amazing,” added Hampton. “I wasn’t expecting anything, but this treatment is working out for me and, for that I am truly blessed,” she said. 

As of December 2020, the clinical trial at Wills Eye is complete and data has been submitted for FDA approval consideration and availability.