NICE recommends Novartis’ Luxturna®▼ (voretigene neparvovec), the first one-time gene therapy for people with vision loss due to RPE65 genetic mutations
Sep 04, 2019
Luxturna (voretigene neparvovec) is a one-time gene therapy and the first and only pharmacological treatment for children and adults in England and Wales who are living with vision loss due to genetic mutations in both copies of the RPE65 gene1
The majority of patients with mutations in both copies of the RPE65 gene will inevitably end up completely blind, placing a huge burden on them, their families and healthcare systems2,3
By providing a working copy of the RPE65 gene, Luxturna (voretigene neparvovec) has the potential to improve vision and prevent patients’ progressive sight loss2
FRIMLEY, UK, September 4th, 2019– Novartis today announced that Luxturna® (voretigene neparvovec) has been recommended for use on the NHS 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 cells4.
Children and adults born with a mutation in both copies of the RPE65 gene can suffer from a range of symptoms from night blindness (nyctalopia), loss of light sensitivity, loss of peripheral vision to loss of sharpness or clarity of vision5, potentially progressing to total blindness2,6.Currently, in the UK, it is estimated that 180 patients have mutations in both copies of the RPE65 gene7-14,with less than 50% diagnosed following a genetic test15.
Voretigene neparvovec is injected under the retina and carries a functioning RPE65 gene to act in place of the faulty one1. It will be the only treatment available in England and Wales for adults and children with this rare progressive genetic condition4.
“We are delighted with today’s decision by NICE to recommend voretigene neparvovec for use in patients with vision loss due to a genetic mutation in both copies of the RPE65 gene” said Haseeb Ahmad, Country President of Novartis UK and Managing Director (UK, Ireland and Nordics) of Novartis Pharmaceuticals. “Through effective collaboration withNICE and NHS England, it has been possible to secure rapid access to the first and only one-time gene therapy for patients living with this condition.”
This is the second time Novartis has worked closely with NICE and NHS England to achieve fast access to a cell and gene therapy. While on average it takes 38 weeks within the Highly Specialised Technologies programme, by working with NHS England and NICE early and constructively this timeline was reduced to 20 weeks – an unprecedented timeframe.
“The patient burden is high for those born with a mutation in both copies of the RPE65 gene. The progressive and debilitating nature of this rare genetic condition places a life-long physical, emotional and financial burden on patients and their families,” said Tina Houlihan, Chief Executive at Retina UK. “NICE’s recommendation of voretigene neparvovec marks a pivotal moment as, for the first time, children and adults born with this condition have a much needed treatment option.”
“The progression of inherited retinal degeneration caused by RPE65 gene mutations leads to blindness, which has a profound effect on the lives of affected patients and their carers” said Robert MacLaren, Professor of Ophthalmology at the University of Oxford and Consultant Ophthalmologist at the Oxford Eye Hospital. “Until now, patients had no other pharmacological treatment options and I am absolutely delighted with the decision by NICE to recommend this one-time gene therapy. As a clinician, I believe the true value of voretigene neparvovec is its potential to improve vision in children and adults, and enabling them to participate fully at school, work and in their private lives.”
The NICE recommendation is based on data from a Phase 1 clinical trial, its follow-up trial, and the first randomised, controlled Phase 3 gene therapy trial for an inherited disease2,16. The primary endpoint of the Phase 3 trial was mean change from baseline to one year in binocular multi-luminance mobility test (MLMT)1. The difference in mean change in binocular MLMT score between patients treated with voretigene neparvovec (n=21) and the control group (n=10) was 1.6 (95% confidence interval: 0.72-2.41; p=0.001). Differences in binocular MLMT performance were observed in the intervention group at day 30 and were maintained over the remaining follow-up visits throughout the four-year period, compared to no change in the control group1,17.
About Luxturna (voretigene neparvovec)
Luxturna (voretigene neparvovec) is the first EU-licenced treatment for this disease and is designed to provide a working copy of the RPE65 gene to act in place of the mutated RPE65 gene16. Voretigene neparvovec is administered as a single injection below the retina in patients who have confirmed RPE65 mutations and viable retinal cells1,2.
Voretigene neparvovec has a durable response, and has the potential to improve vision and prevent progressive sight loss2,17,18. Patients who received voretigene neparvovec 4 years ago in the Phase 3 study show sustained benefit on functional vision18. Additionally, patients who received voretigene neparvovec in the Phase 1 study continue to experience sustained improvement in light sensitivity – which correlates well with functional vision – 7.5 years after treatment17. Longevity of response will be part of long-term follow up observations.
About RPE65 mutation-associated inherited retinal disease
RPE65 is one out of more than 260 genes that may be responsible for an RPE65-mediated inherited retinal disease16. Mutations in both copies of the RPE65 gene can lead to blindness3. Patients can suffer from night blindness (nyctalopia), loss of light sensitivity, loss of peripheral vision, loss of sharpness or clarity of vision, impaired dark adaptation and repetitive uncontrolled movements of the eye (nystagmus)5. Patients with mutations in both copies of the RPE65 gene may commonly be clinically diagnosed with forms of either Leber congenital amaurosis or retinitis pigmentosa13.
About Luxturna’s (voretigene neparvovec’s) mechanism of action
Voretigene neparvovec is the first EU-licensed treatment for this disease and is designed to provide a working copy of the RPE65 gene to act in place of the mutated RPE65 gene16.
About the Novartis and Spark Therapeutics licensing and supply agreement
In January 2018, Spark Therapeutics entered into a licensing and supply agreement with Novartis covering development, registration and commercialization rights to Luxturna in markets outside the US. Commercialization rights in the EU/EEA are now assigned to Novartis following the successful completion of the marketing authorization transfer by Spark Therapeutics. Novartis already has exclusive rights to pursue development, registration and commercialization in all other countries outside the US, and Spark Therapeutics will supply the gene therapy to Novartis.
About Novartis and ophthalmology
For more than 70 years, patients, caregivers and healthcare providers worldwide have looked to Novartis for state-of-the-art treatments in eye diseases. We continue to invest in science as well as in strategic alliances to help ensure patients have access to screening, diagnosis, and our eye medicines. Our commitment to vision extends globally across ages, from premature infants to seniors, from rare diseases to those affecting millions, from eye drops to gene therapies. Our aspiration: reimagining eye care to help everyone see possibilities.
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 105 000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com.
In the UK, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis. Since 2014, Novartis has invested over £200 million in R&D and is a leading sponsor of clinical trials, in the UK. For more information, please visit www.novartis.co.uk
Russell S et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65- mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet 2017; 390:849-860.
Khan, Z., Braich, P. S., Rahim, K., Rayat, J. S., Xing, L., Iqbal, M., … Almeida, D. (2016). Burden and Depression among Caregivers of Visually Impaired Patients in a Canadian Population. Advances in Medicine, 2016, 1–8. https://doi.org/10.1155/2016/4683427
Bundley and Crews. A study of retinitis pigmentosa in the City of Birmingham. I Prevalence. Journal of Medical Genetics, 1984; 21, 417-420.
Bertelsen M et al. Prevalence of Generalized Retinal Dystrophy in Denmark. Ophthalmic Epidemiology, 2014; 21, 217-223.
Stone EM. Leber Congenital Amaurosis–A Model for Efficient Genetic Testing of Heterogeneous Disorders: LXIV Edward Jackson Memorial Lecture. Am J Ophthalmol, 2007; 144, 791-811.
Morimura H et al. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis. Proceedings of the National Academy of Sciences of the USA. 1998; 95: 3088–93.
Wang, F., et al., Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements. Human genetics, 2014. 133(3): p. 331-345.
Bocquet, B., et al., Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations. Molecular Vision, 2013. 19: p. 2487-2500.
Henderson, R.H., et al., An assessment of the apex microarray technology in genotyping patients with Leber congenital amaurosis and early-onset severe retinal dystrophy. Investigative Ophthalmology & Visual Science, 2007. 48(12): p. 5684-5689
Chung D et al. Long-term effect of voretigene neparvovec on the full-field light sensitivity threshold test of patients with RPE65 mutation-associated inherited retinal dystrophy: post-hoc analysis of phase I trial data. Presented at ARVO 2019.
Russell S et al. Three-year update for the phase 3 voretigene neparvovec study in biallelic RPE65 mutation-associated inherited retinal disease. Investigative Opthalmology & Visual Science, 2018; 59.