Three-year Follow-up Phase 3 Data Provide Additional Information on Luxturna in Patients with Biallelic RPE65-Mediated Inherited Retinal Disease

Source: Spark Therapeutics

Friday, November 10, 2017 | Clinical Trials , Retina , Spark Therapeutics


Spark Therapeutics announced new 3-year follow-up data from the continuing phase 3 trial of Luxturna (voretigene neparvovec), an investigational, potential one-time gene therapy for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease (IRD). These data were presented at the American Academy of Ophthalmology (AAO) Retina Subspecialty Day by Albert M. Maguire, MD, a principal investigator of the phase 3 clinical trial, professor of ophthalmology at the Scheie Eye Institute at the University of Pennsylvania’s Perelman School of Medicine and attending physician in the Division of Pediatric Ophthalmology at Children's Hospital of Philadelphia.

“These data provide additional support information on the efficacy, durability and safety of investigational Luxturna, showing no statistically significant change in the primary endpoint from the initial gain in functional vision at the three-year time point for the original intervention group and at the two-year time point for the original control group after crossover,” Katherine High, MD, president and head of Research and Development at SparkTherapeutics, said in a company news release. “We believe the data from these participants further support the positive benefit-risk profile of investigational Luxturna for patients with vision loss due to confirmed biallelic RPE65-mediated IRD.”

Functional vision is considered a key component in a person’s ability to perform daily living tasks and can be assessed through orientation and mobility testing and other measurements.

Three years after the one-time administration of investigational Luxturna to both eyes, the cohort of 20 participants in the modified intent-to-treat (mITT) intervention group maintained the average improvement demonstrated at 1 year, as measured by multi-luminance mobility test (MLMT) score change, the primary endpoint, and full-field light sensitivity threshold (FST) testing, a secondary endpoint. The mean MLMT improvement measured 1.8 lux levels at three years, compared to 1.9 lux levels at one year. The more than 100-fold average improvement in FST testing observed in the intervention group at one year similarly was maintained through at least three years. Additionally, the increase in visual acuity (VA) averaged over both eyes, a secondary endpoint which was not statistically significant at one year, has been stable for at least 3 years for participants in the intervention cohort, at an eight-letter improvement using standardized AV testing. 

The mean change from baseline in Goldmann III4e test stimulus, a prespecified exploratory measure of visual field (VF), was 282.2 sum total degrees averaged over both eyes for participants in the intervention group at the 3-year time point, compared to a mean change of 302.1 sum total degrees at 1 year.

Likewise, all participants in the control group (n=9), who after one year of undergoing observation with the same retinal and visual function testing as the original intervention group elected to cross over and receive Luxturna in both eyes, maintained the same mean MLMT score change of 2.1 lux levels 1 year following the one-time injection through 2 years after administration. The more than 100-fold average improvement in FST testing observed in the crossover group at one year similarly was maintained through at least 2 years.

Similarly, in the crossover group, the increase in VA averaged over both eyes, was not statistically significant at one year, but has remained improved compared to baseline for at least 2 years.

The mean change from baseline in Goldmann VF was 182.6 sum total degrees averaged over both eyes for participants in the crossover group at the 2-year time point, compared to a mean change of 194.3 sum total degrees at 1 year.

No new serious adverse events (SAEs) associated with Luxturna or deleterious immune responses were observed.Most ocular adverse events (AEs) were mild in severity, with the most common being cataract, elevated intraocular pressure, retinal deposits and retinal tears. One participant in the crossover group experienced an SAE related to the surgical procedure in which there was foveal thinning and a sustained reduction in VA. Three participants in the intervention group had SAEs unrelated to study participation.

Luxturna is under Priority Review with the FDA, with an assigned Prescription Drug User Fee Act (PDUFA) date of Jan. 12, 2018. In October 2017, FDA’s Cellular, Tissue and Gene Therapies Advisory Committee unanimously recommended (16-0) approval of Luxturna. The advisory committee’s recommendation is non-binding, but FDA generally considers such recommendations when reviewing a Biologics License Application (BLA). Luxturna has received orphan drug, breakthrough therapy and rare pediatric disease designations from FDA.

In August 2017, Spark Therapeutics’ Marketing Authorization Application (MAA) for Luxturna was validated by European Medicines Agency (EMA). Luxturna also has received orphan product designations from EMA.


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