Spark Therapeutics (ONCE) Says Data Reinforces Efficacy and Durability of Voretigene Neparvovec in RPE65-Mediated Inherited Retinal Disease

October 14, 2016 1:21 PM EDT

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Spark Therapeutics (NASDAQ: ONCE), a fully integrated gene therapy company seeking to transform the lives of patients with debilitating genetic diseases by developing investigational, potentially one-time, life-altering treatments, announced today that Principal Investigator Albert M. Maguire, M.D., professor of ophthalmology at the Perelman School of Medicine of the University of Pennsylvania, presented one-year efficacy data from the crossover group and two-year durability data from the original intervention group for the Phase 3 trial of voretigene neparvovec (formerly SPK-RPE65) during Retina Subspecialty Day at the American Academy of Ophthalmology 2016 Annual Meeting in Chicago.

Voretigene neparvovec, an investigational gene therapy for Inherited Retinal Disease (IRD) caused by mutations in the RPE65 gene, has received both breakthrough therapy and orphan product designations from the U.S. Food and Drug Administration (FDA), as well as orphan product designations from the European Medicines Agency (EMA).

The crossover group consists of nine subjects who, after one year of undergoing the same retinal and visual function testing as the original intervention group, elected to cross over and receive voretigene neparvovec in both eyes. One year after administration, the mean improvement among all nine subjects, as measured by the primary endpoint, a multi-luminance mobility test (MLMT), was 2.1 lux levels.

Dr. Maguire also presented data that showed that the original intervention group subjects who received voretigene neparvovec (n=20) maintained improvement demonstrated at year one, as measured in MLMT and full-field light sensitivity threshold (FST) testing, for at least two years. The mean MLMT improvement of 1.9 lux levels was sustained after two years. The more than 100-fold average improvement in FST testing observed in the original intervention group at one year similarly was maintained through at least two years.

“Results from the ongoing Phase 3 trial of voretigene neparvovec show that 93% of subjects, including those in the original control group who crossed over to receive intervention, demonstrated a gain in functional vision, and maintained that improvement over one year following the procedure,” said Dr. Maguire. “Additionally, the original intervention group sustained its year one improvement at year two. These data further bolster the growing dataset supporting voretigene neparvovec.”

Visual Field Data Show Statistical Significance Across Two Measures For the first time, Dr. Maguire presented data on visual field (VF), another protocol-specified endpoint in the Phase 3 trial of voretigene neparvovec. VF is total field area of a person’s retinal sensitivity, or vision, that extends from a central fixation point to the periphery. Data collected using two VF measures showed statistically significant responses.

“Using the Goldmann III4e test stimulus, the visual field area of the original intervention group showed significant improvement, nearly doubling at year one, while a slight decrease in visual field area was observed in the control group,” said Dr. Maguire.

Using the Goldmann III4e test stimulus, the intervention group saw a mean increase of 302.1 sum total degrees from baseline at year one, while the control group saw a mean decrease of 76.7 sum total degrees, resulting in a difference of 387.7 sum total degrees (nominal p=0.006). Additionally, using the Humphrey macula threshold measure, the visual field increased by a mean of 7.7 decibels (dB) from baseline for the intervention group, compared to a decrease of 0.2 dB for the control group, resulting in a difference of 7.9 dB (nominal p<0.001).

“The visual field data clearly demonstrate the effect of the investigational therapy on a well-understood clinical endpoint and we will be further examining these data over the next few months,” said Katherine A. High, M.D., president and chief scientific officer, Spark Therapeutics.

Voretigene Neparvovec Phase 3 Trial OverviewThe Phase 3 trial for voretigene neparvovec includes an original intervention group of 20 subjects who had voretigene neparvovec administered in both eyes and a control group of nine subjects. All nine control subjects elected to “cross over” and have voretigene neparvovec administered following one year of the same retinal and visual function testing of the original intervention group. The mITT population (n = 29) includes all subjects who received voretigene neparvovec, either in the original intervention group or in the crossover group of the Phase 3 trial.

Findings from the original intervention group announced in the fall of 2015 include statistically and clinically significant improvement compared to the control group on the primary endpoint, measured in change in MLMT between baseline and one year. The first two secondary endpoints – FST for white light and MLMT for the assigned first eye – also showed highly statistically significant improvement. A third secondary endpoint, visual acuity, did not meet statistical significance.

Safety results in the voretigene neparvovec clinical program have been consistent to date. No serious adverse events (SAEs) associated with voretigene neparvovec or deleterious immune responses have been observed. There was one SAE in one eye of a Phase 3 crossover group subject, which was determined to be related to the surgical procedure, rather than to the product candidate. The subject exhibited foveal thinning and a reduction in visual acuity after the surgical procedure that did not return to baseline but did show an improvement on the MLMT and also exhibited a gain in FST. An additional SAE related to participation in the clinical studies occurred in one eye of a Phase 1 follow-on study subject; in this case, the treatment for bacterial endophthalmitis led to elevated intraocular pressure and subsequent optic atrophy.

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