Novartis receives European licence for Luxturna®▼ (voretigene neparvovec), the first one-time gene therapy to improve visual acuity in people with rare inherited retinal disease
Nov 22, 2018
Voretigene neparvovec is the first licensed gene therapy to treat an inherited retinal disease, indicated for children and adults with vision loss caused by mutations in both copies of the RPE65 gene and who have sufficient viable retinal cells1
Nearly 60% of patients have severe forms of the disease, with severe visual impairment occurring shortly after birth2
Frimley, UK, 23 November, 2018 – Novartis today announced that the European Medicines Agency (EMA) has granted a licence for the use of Luxturna®* (voretigene neparvovec), a one-time gene therapy for the treatment of patients with vision loss due to a genetic mutation in both copies of the RPE65 gene and who have enough viable retinal cells1.
Children born with mutations in both copies of the RPE65 gene will experience sight loss from an early age, with the majority of patients progressing to total blindness3,4. Research shows that vision impairment and blindness in children frequently cause social isolation, emotional distress, loss of independence, or hazards such as falls and injuries4.
Currently in the UK, it is estimated that 337 people have inherited retinal disease (IRD) and mutations in both copies of the RPE65 gene5-12. The working copy of the RPE65 gene provided by voretigene neparvovec has the potential to improve visual acuity in children and adults with sufficient viable retinal cells3.
The EC decision is based on a positive CHMP opinion that looked at data from a Phase 1 clinical trial, its follow-up trial, and the first randomised, controlled Phase 3 gene therapy trial for an inherited disease3. The primary endpoint of the Phase 3 study was mean change from baseline to one year in binocular multi-luminance mobility testing (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). Significant 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 three-year period, compared to no change in the control group1.
“This is a significant clinical advance and marks a milestone in Novartis’ journey toward bringing potentially life-changing cell and gene therapies in ophthalmology,” said Dr Mark Toms, Chief Scientific Officer, Novartis Pharmaceuticals UK. “Novartis is committed to re-imagining care for people affected by this disease and ensuring current and future patients who may benefit from this therapy have timely access to it.”
Initial decisions on voretigene neparvovec for patients with vision loss due to a genetic mutation in both copies of the RPE65 gene from the Scottish Medicine Consortium (SMC) and the National Institute for Health and Care Excellence (NICE) are expected in 2019. Novartis is working closely with all stakeholders to help ensure that eligible patients can start benefitting from this treatment as quickly as possible.
A range of resources and innovative reimbursement and access approaches are also being explored in order to provide as much support as possible to both patients and healthcare professionals.
About RPE65 mutation-associated inherited retinal disease Inherited retinal diseases are a group of rare blinding conditions caused by more than 260 different genes13, often disproportionally affecting children and young adults3. Mutations in both copies of the RPE65 gene affect approximately 1 in 200,000 people14.
Mutations in both copies of the RPE65 gene can lead to blindness. Early in the disease 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)15. Patients with mutations in both copies of the RPE65 gene may be diagnosed, for instance, with subtypes of either Leber congenital amaurosis or retinitis pigmentosa11. A genetic test is needed to confirm that vision loss is caused by mutations in the RPE65 gene3.
About the multi-luminance mobility test (MLMT) The MLMT measures changes in patient relevant functional vision by asking patients to navigate a course accurately and at a reasonable pace at seven different levels of illumination, ranging from 400 lux (corresponding to a brightly lit office) to one lux (corresponding to a moonless summer night)1,3.
About Luxturna (voretigene neparvovec) 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 gene1,3. Voretigene neparvovec is administered as a single injection below the retina in patients who have confirmed RPE65 mutations and viable retinal cells1,3.
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 commercialisation rights to voretigene neparvovec in markets outside the US. Commercialisation rights in the EU/EEA will be assigned to Novartis upon successful completion of the Marketing Authorisation transfer by Spark Therapeutics. Novartis already has exclusive rights to pursue development, registration and commercialisation in all other countries outside the US, and Spark Therapeutics will supply the gene therapy to Novartis.
About Novartis in 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.
About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 125,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.
In the UK, Novartis develops and markets innovative medicines, devices and diagnostic tests which help improve patient outcomes. Based on four sites across the north and south of England, 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 by manufacturing the active pharmaceutical ingredients used worldwide in many medicines. In 2017 Novartis invested almost £30million 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.
Bundley and Crews. A study of retinitis pigmentosa in the City of Birmingham. I Prevalence. Journal of Medical Genetics, 1984; 21, 417-420.
Bunker C H et al. Prevalence of Retinitis Pigmentosa in Maine. Am J Ophthalmol,1984; 97, 357-65.
Bertelsen M et al. Prevalence of Generalized Retinal Dystrophy in Denmark. Ophthalmic Epidemiology, 2014; 21, 217-223.
Haim M. The epidemiology of retinitis pigmentosa in Denmark. Acta Ophthalmologica Scandinavica, 2002; 233, 1-34.
Haer-Wigman L et al. Diagnostic exome sequencing in 266 Dutch patients with visual impairment. European Journal of Human Genetics, 2017; 25, 591-599.
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.