Spark Therapeutics (NASDAQ:ONCE), a gene therapy company based in Philadelphia, USA, has announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency for Investigational “LUXTURNA” (voretigene neparvovec). The gene therapy treatment, designed for patients with vision loss due to Leber’s congenital amurosis, has similarly undergone regulatory submission in the United States. According to the company, the MAA in Europe includes data from three clinical trials comprising 41 patients in total, representing the first randomized, controlled Phase 3 trial for a gene therapy for a genetic disease.
The proposed treatment underwent two open-label Phase 1 trials between 2007 and 2012, and a more recent single open-label, randomized, controlled Phase 3 trial. According to the company, subsequent to a one-year control period in the Phase 3 study, all control participants elected to cross over and receive treatment and all particpants of the study will now undergo continual follow up to assess long-term safety and efficacy. All patients participating in the trials were aged between 4 years and 44 years at the time of first administration and each patient had confirmed biallelic RPE65 mutations as part of the eligibility criteria. Results of the clinical studies, previously reported in the medical journal, The Lancet, showed a statistically significant and clinically meaningful difference between intervention (n=21) and control participants (n=10) at one year and in the mean bilateral multi-luminance mobility testing (MLMT) change score (difference of 1.6; 95% CI, 0.72, 2.41; p=0.0013). According to the company, 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 full-field light sensitivity threshold (FST). Results from the study indicated a more than 100-fold (or > 2 log units) average improvement in FST testing observed in the original intervention group at one year which appera to be similarly maintained through at least two years.
The milestone has been recognised as a significant achievement in both the fields of gene therapy and retinal disease. Christina Fasser, President of Retina International, an umbrella organization of more than 43 patient organizations, commented that the announcement from Spark, “represents an important moment in the effort to treat blindness caused by inherited retinal degenerative diseases. We are excited about the potential of this application to bring the first gene therapy to patients with this form of IRD.”