LuxturnaVision loss due to Leber congenital amaurosis or retinitis pigmentosa caused by confirmed biallelic RPE65 mutations
New molecular entity
Development and Regulatory status
Feb 20First patient receives Luxturna gene therapy in the UK (at Moorfields Eye Hospital) .
Dec 19Spark Therapeutics was acquired by Roche 
Sep 19NHS England announces funding for voretigene after reaching a NICE-endorsed deal with Novartis to fund the drug, which costs £613,410 per patient at full price. Access is expected to be in place from January 2020, where the treatment will initially be available from three national specialist centres across the UK, with the option to roll-out the treatment to other hospitals .
Nov 18Approved in EU .
Sep 18Recommended for EU approval by CHMP - the full indication is "for the treatment of adult and paediatric patients with vision loss due to inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations and who have sufficient viable retinal cells.” It is proposed that Luxturna be administered by a retinal surgeon experienced in performing macular surgery.
Jan 18Spark Therapeutics have entered a licensing and supply agreement with Novartis to develop and commercialise voretigene neparvovec outside the US. Under the agreement, Spark will retain regulatory responsibility for obtaining European Medicines Agency approval for voretigene neparvovec, which is expected Q3 2018 .
Jan 18Spark announce price in the US will be $850,000 ($425,000 per eye) .
Dec 17Approved by FDA for treatment of pediatric and adult patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy .
Oct 17An FDA Advisory Committee unanimously recommended approval of Luxturna (voretigene neparvovec) for pts with Biallelic RPE65-mediated Inherited Retinal Disease .
Aug 17Spark has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for LUXTURNA™, the proposed trade name for voretigene neparvovec .
Aug 16US licence application ongoing. The company announced its intention to submit clinical components of the BLA by end of year and the CMC components by early 2017 .
May 16Spark Therapeutics announced that it has submitted the first component, the non-clinical component, as part of its rolling BLA submission with the US FDA. This will be followed by the clinical module and then the CMC (chemistry, manufacturing and controls) module .
Apr 16Advanced Therapy IMP 
Mar 16Spark Therapeutics anticipates filing a Marketing Authorisation Application (MAA) with the EMA in early 2017. The company has received positive written scientific advice from the EMA .
Oct 15Spark intends to file a Biologics License Application with the FDA in 2016 as the first step in executing its global regulatory and commercialisation strategy .
Nov 14SPK-RPE65 receives breakthrough therapy designation from US FDA for treatment of nyctalopia (night blindness) in pts with Leber congenital amaurosis (LCA) due to mutations of the RPE65 gene. This follows orphan product designation in both the US and EU. Spark expects to report data from its Phase 3 trial in the second half of 2015 and file a Biologics License Application with FDA in 2016 [3,4].
Jan 14Company report it has reached the patient recruitment goal in its PIII trial and anticipates filing for approval in the US in 2015 .
Gene therapy, delivering functional RPE65 gene via subretinal administration to both eyes via surgical procedures on separate days
Inherited retinal dystrophies (IRDs) are a group of rare eye disorders that may be caused by numerous gene mutations, and include retinitis pigmentosa (approx 50% of all IRDs) and Lebers congenital amaurosis (approx 5% of IRDs). RPE65 gene mutations are associated with approx 2% of RP cases and 6-16% LCA cases. Worldwide prevalence of RP is 1 in 4,000 births and of LCA is 2-3 in 100,000 births.
Vision loss due to Leber congenital amaurosis or retinitis pigmentosa caused by confirmed biallelic RPE65 mutations
Trial or other data
Oct 19Voretigene neparvovec is recommended by NICE, within its marketing authorisation, as an option for treating RPE65-mediated inherited retinal dystrophies in people with vision loss caused by inherited retinal dystrophy from confirmed biallelic RPE65 mutations and who have sufficient viable retinal cells. It is recommended only if the company provides voretigene neparvovec according to the commercial arrangement .
Sep 19Draft NICE guidance recommends voretigene neparvovec (VN), within its marketing authorisation, as an option for treating people with vision loss caused by inherited retinal dystrophies from confirmed biallelic RPE65 mutations and who have sufficient viable retinal cells, if the company provides VN according to the commercial arrangement .
Dec 17This offers a potentially sight-improving, long-lasting treatment for patients with no other effective options. Delivery is likely to be from specialist centres for carefully selected patients. First FDA approved gene therapy to targets a disease caused by a specific gene mutation.
Jul 17Results of NCT00999609 published in The Lancet .
Oct 15Spark presents additional data from the PIII pivotal trial as well as continued durability data from an earlier PI study. There was a mean improvement in functional vision of intervention subjects (n=20) of 1.9 specified lux levels vs. an improvement of 0.2 specified lux levels in control subjects (n=9) as measured by change in bilateral mobility testing (MT) between baseline and one year in the modified intent-to-treat (mITT) population. The mITT population (n=29) includes all subjects that received SPK-RPR65, and only those who continued beyond the baseline study visit. Two subjects in the intent-to-treat (ITT) population (n=31) that were randomised but never received SPK-RPE65 are excluded from this efficacy analysis population. Thirteen of the 20 subjects receiving SPK-RPE65 were able to pass the MT at one lux at year one, demonstrating maximum improvement measurable on the MT score. None of the nine control subjects followed was able to pass MT at one lux at year one. In a corresponding finding in the first secondary efficacy endpoint, full-field light sensitivity threshold testing (FST) for white light, intervention subjects demonstrated a highly statistically significant mean improvement of -2.06 log10(candela second/m2) vs. decline of 0.04 log10 (candela second/m2) among control subjects (all analyses in mITT population) .
Oct 15Spark Therapeutics announces positive top-line results from the PIII pivotal trial of SPK-RPE65 for treatment of RPE65-mediated inherited retinal dystrophies (IRDs). The trial met its primary endpoint (p=0.001), demonstrating improvement of functional vision in the intervention group compared to the control group, as measured by the change in bilateral mobility testing between baseline and one year. There were no serious adverse events related to SPK-RPE65 or deleterious immune responses observed in the trial. Overall, adverse events related to the administration procedure were consistent with observations in earlier studies of SPK-RPE65. In addition, subjects who received SPK-RPE65 outperformed control subjects across the first two secondary endpoints: full-field light sensitivity threshold testing (p<0.001) and the mobility test change score for the first injected eye (p=0.001). The third secondary endpoint, visual acuity, did not show statistically significant evidence of benefit (p=0.17). All reported p-values reflect results from the intent-to-treat (ITT) population, the most stringent efficacy analysis population described in the statistical analysis plan (SAP) .
Feb 15NCT00999609 is ongoing, but not recruiting participants
Jan 14NCT00999609 is a PIII open-label, randomized controlled trial in 24 subjects with Leber Congenital Amaurosis (LCA) using adeno-associated viral vector to deliver the gene for human rpe65 to the retinal pigment epithelium. The primary outcome is mobility testing at 1 year; secondary outcomes include additional visual/retinal function tests. AAV2-hRPE65v2 (1.5E11 vector genomes per eye) will be administered subretinally to both eyes via surgical procedures on separate days. The study started in 2012 and is due to complete 2029 (primary outcome data collection Apr 15) .