Spark Therapeutics: Lancet publishes Phase 3 data of voretigene neparvovec
Spark Therapeutics announced The Lancet has published Phase 3 clinical trial data of voretigene neparvovec, an investigational, potential one-time gene therapy candidate for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease. In the trial, investigational voretigene neparvovec improved functional vision, light sensitivity and visual field in study participants with RPE65-mediated IRD. A natural history study has shown that people with this IRD eventually progress to complete blindness. The publication presents the results of the Phase 3 trial, including the intent-to-treat population of all randomized subjects, through the one-year timepoint. Results showed a statistically significant and clinically meaningful difference between intervention (n=21) and control participants (n=10) at one year, per the clinical trial's primary endpoint, mean bilateral multi-luminance mobility testing change score (difference of 1.6; 95% CI, 0.72, 2.41; p=0.0013). Participants maintained functional gains observed 30 days post-administration at the one-year primary endpoint. MLMT evaluates functional vision by documenting the participants' ability to navigate a mobility course under a variety of specified light levels ranging from one lux (equivalent to, for example, a moonless summer night) to 400 lux (equivalent to, for example, an office environment). Improvements seen in MLMT were accompanied by statistically significant improvements in two secondary endpoints, including full-field light sensitivity threshold testing averaged over both eyes (p=0.0004). A third secondary endpoint, the change in visual acuity averaged over both eyes, was not statistically significant between intervention and control participants (p=0.17). An additional protocol-specified endpoint using the Goldmann III4e test stimulus to measure the visual field area of the original intervention group showed significant improvement (p=0.0059), nearly doubling at year one, while a slight decrease was observed in the control group over the same time period. No serious adverse events associated with voretigene neparvovec or deleterious immune responses were observed. Most ocular events were mild in severity with the most common ocular adverse events being transient mild ocular inflammation, transient elevated intraocular pressure, cataracts and intraoperative retinal tears. Two participants in the intervention group, one with a pre-existing complex seizure disorder and another who experienced complications from oral surgery, had SAEs unrelated to study participation.