Following Australian Federal and State Government funding, Luxturna (voretigene neparvovec) has become the first ocular gene therapy to be made widely available for the treatment of patients with inherited retinal disease (IRD) caused by pathological biallelic RPE65 mutations and who have sufficient viable retinal cells as determined by the treating physician.1 Prior to the approval of Luxturna, there were no treatment options for people with this rare progressive, genetic condition; patients could not escape the lifelong burden of the disease and the majority had to prepare for total blindness.2
Distributed in Australia by Novartis, the funding follows a review and positive recommendation from the Medical Services Advisory Committee (MSAC) and working closely with the States and Territories under the National Health Reform Agreement (NHRA).3 The Royal Victorian Eye and Ear Hospital has been announced by the Victorian Government as the designated Victorian provider of Luxturna, for eligible patients under the 2021–25 NHRA.
Luxturna is a one-time injection designed to directly address the genetic root cause of IRD by replacing the faulty RPE65 gene.1 This gene is responsible for making a protein (known as RPE65) that is essential for normal vision.4 As a highly complex therapy, Luxturna is typically delivered via an injection behind the retina, by a specialised retinal surgeon.
IRD, associated with the RPE65 mutation, is a rare and devastating disease affecting ~1 in 200,000 people – the equivalent of 125 Australians.5 For those born with IRD, the burden of disease is high; with progressive loss of sight over time, most become blind by the time they become a teenager.6-9
Research shows vision impairment and blindness in children frequently causes social isolation, emotional distress, loss of independence, and hazards such as falls and injuries.8 Luxturna reduces the burden of disease for patients and families by replacing a lifetime of care with one single treatment.1
“The funding of Luxturna, the first ocular gene therapy to be available to people with an inherited retinal disease caused by mutations in the RPE65 gene, marks a new era of treatment in Australia,” said Dr Tom Edwards, Clinical Lead for implementation of Luxturna, a vitreoretinal surgeon at The Royal Victorian Eye and Ear Hospital and Principal Investigator of Retinal Gene Therapy Research at the Centre for Eye Research Australia (CERA). “Gene therapy introduces the potential to improve vision and prevent progressive sight loss in those with a genetic mutation following a single injection into each eye.”
The registration and funding decision 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 IRD.2 In the Phase 3 clinical trial, vision improvement was recorded as early as 30 days after treatment.2 At one year, compared with the control group, patients treated with Luxturna improved by 1.6 light levels on the binocular multi-luminance mobility test (MLMT), the trial’s novel, patient-centric, primary endpoint.2 Vision improved by one or more light levels for 90% of patients treated with Luxturna, and 65% were able to successfully navigate the MLMT at the lowest light level of one lux at one year. Luxturna reports a favourable safety profile; data from all patients in the Phase 1 follow-on and Phase 3 studies demonstrate that the intervention has a safety profile consistent with the surgical procedure required to administer the treatment.10
Early on, patients with RPE65 mutations 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 vision.6,11 The progressive loss of vision over time with a mutation in both copies of the RPE65 gene highlights the urgent need for early genetic diagnosis and treatment.12
- Luxturna (Voretigene neparvovec) Product Information, March 2022. Available at: www.guildlink.com.au/gc/ws/nv/ pi.cfm?product=nvpluxin
- Russell S, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) inpatients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled,open-label, phase 3 trial. The Lancet 2017; 390:849–860.
- MSAC Public Summary Document – November 2020 www. msac.gov.au/internet/msac/publishing.nsf/Content/925970 AEEB124D57CA258536000ED370/$File/1623%20Final%20 PSD_Nov2020_redacted.pdf
- MedLine Plus. RPE65 gene. Available via: medlineplus.gov/ download/genetics/gene/rpe65.pdf. Accessed August 2021
- Novartis. Data on file. 2018.
- Chung DC, et al. The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene. Am J Ophthalmol 2019;199: 58–70.
- Banhazi J et al. PSY195 – Humanistic burden associated with RPE65 gene mutation related inherited retinal dystrophies: a systematic literature review. Value in Health 2018;21(3):S469.
- Banken, R et al. Voretigene Neparvovec for Biallelic RPE65-Mediated Retinal Disease: Effectiveness and Value, Final Evidence Report. Institute for Clinical and Economic Review 2018. Available at https://icer-review.org/wp-content/ uploads/2017/06/mwcepac_voretigene_final_evidence_ report_02142018.docx.pdf. Last accessed November 2018.
- Khan Z et al. Burden and Depression among Caregivers of Visually Impaired Patients in a Canadian Population. Advances in Medicine, 2016, 1–8.
- Maguire AM et al. Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials. Ophthalmology 2019;126:1273-1285.
- Astuti GD, et al. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark. Eur J Hum Genet 2016; 24:1071–79.
- Bennett J et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. The Lancet. 2016;388(10045):661-672.