Cure for Inherited Retinal Dystrophies on the Horizon

Source: American Academy of Ophthalmology

Sunday, November 12, 2017 | Medical Studies , American Academy of Ophthalmology


A groundbreaking retinal gene replacement therapy shows continued success in improving functional vision in patients with RPE65-mediated retinal dystrophies, according to trial data presented by Albert M. Maguire, MD, on Friday at the Retina Subspecialty Day.

“Gene therapy with voretigene neparvovec improved functional vision and visual function as measured by ambulatory navigation, light sensitivity, and visual field size,” said Dr. Maguire.

The phase 3 trial reported 3-year outcomes of 20 patients with autosomal-recessive mutations in the RPE65 gene who received a single injection of voretigene neparvovec (Luxturna, Spark Therapeutics) in each eye. Also included were 2-year results for 9 patients who served as untreated controls during the first year of the study and subsequently elected to cross over and receive treatment. 

Evaluating real-world improvements.

The primary outcome measure was change from baseline score in bilateral multi-luminance mobility testing (MLMT), a novel walking maze that assesses aspects of visual field, light perception, and contrast sensitivity. 

The navigation test was done under 7 standardized light levels that correlate to light conditions found in daily life, ranging from a dark, moonless night (1 lux) to that of an office building (400 lux). There were 12 different versions of the mobility course to eliminate the possibility of improvement through learning effect.

Sustained efficacy.

Three years after voretigene injections, 69% of all subjects and 89% of the delayed intervention subjects were able to pass the MLMT at 1 lux, demonstrating the maximum measurable improvement. At baseline, none had been able to complete the maze at 1 lux.  

Earlier this year, 2-year study results published in the Lancet showed that 65% of the original intervention group had achieved the MLMT at 1 lux. The new data confirm that the  efficacy of the gene therapy was not only maintained but possibly even improved between years 2 and 3.

“Subjects in the original intervention group treated with voretigene had a mean change in white light sensitivity at year 3 of greater than 2 log units compared to baseline; this is more than 100-fold improvement in light sensitivity,” said Dr. Maguire. “Subjects in the delayed intervention group had a near 500-fold increase. Again, notice the durability of improvement.”

No significant difference in visual acuity was found, which is not unexpected for this rod-mediated disease.

The road to approval.

Spark Therapeutics has submitted a new biologics license application for Luxturna, and the FDA’s decision is expected before Jan. 12, 2018.—Aliyah Kovner

Financial disclosures. Dr. Maguire: Foundation Fighting Blindness: S; Regenxbio Inc: C,S; Spark Therapeutics: S,C.

Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.


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