Spark Therapeutics Submits Marketing Authorization Application to European Medicines Agency for Investigational LUXTURNA(TM) (voretigene neparvovec) - Seite 2

Clinical Trial Overview of LUXTURNA(TM) (voretigene neparvovec)
The safety and efficacy of LUXTURNA were assessed in two open-label Phase 1 trials, which continue to follow participants who received LUXTURNA between 2007 and 2012, and one open-label, randomized, controlled Phase 3 trial. Following the one-year control period of the Phase 3 study, all control participants elected to cross over and received LUXTURNA; long-term safety and efficacy continue to be assessed in the Phase 3 participants who received LUXTURNA between 2013 and 2015. The clinical trial program included 41 participants with vision loss aged four to 44 at the time of first administration. Confirmed biallelic RPE65 mutations and the presence of sufficient viable retinal cells were established in all participants.

LUXTURNA Phase 3 clinical trial data, including data from the intent-to-treat population of all randomized participants through the one-year time point, were published in The Lancet. Results reported in The Lancet 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 (MLMT) change score (difference of 1.6; 95% CI, 0.72, 2.41; p=0.0013). In addition, participants who received LUXTURNA showed a marked difference compared to control participants across the first two secondary endpoints: full-field light sensitivity threshold (FST) testing averaged over both eyes (p=0.0004) and the mobility test change score for the first injected eye (p=0.0005). A third secondary endpoint, the change in visual acuity (VA) averaged over both eyes, was not statistically significant between intervention and control participants (p=0.17).

On average, participants in the original Phase 3 intervention group maintained functional gains observed by the day-30 visit through at least two years, as measured by MLMT and FST. The more than 100-fold (or greater than two log units) average improvement in FST testing observed in the original intervention group at one year, similarly, was maintained through at least two years.

In continuation of the trial to include crossover of the control group to receive LUXTURNA, 93 percent (27 of 29) of all Phase 3 trial participants injected with LUXTURNA saw a gain of functional vision as assessed by bilateral MLMT over the follow-up period of at least one year from administration of LUXTURNA to each eye. Additionally, 72 percent (21 of 29) of all Phase 3 trial participants receiving LUXTURNA successfully completed MLMT at the lowest light level evaluated (1 lux) at one year.