Luxturna, the first approved gene therapy for an IRD,1 is a one-time treatment that introduces a functioning RPE65 gene into the retina, restoring the visual cycle2
- Luxturna is an approved gene therapy 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.1
Luxturna uses gene augmentation to deliver a working copy of the RPE65 gene to the retinal pigment epithelium (RPE) cells.1
- Delivered in vivo by subretinal injection (at 4 commissioned treatment centres in the UK).1
- Genetic material delivered using adeno-associated virus vector which has low immunogenicity when delivered subretinally.1
- Introduced gene remains separate to patient's own DNA and restricted to the cells of the eye.1
- A genetic test is essential to determine eligibility.1,2
Luxturna safety and efficacy were assessed in an open-label controlled Phase III trial1–3
Adults and children (4–44 years) with an IRD and confirmed biallelic RPE65 mutations and sufficient viable retinal cells.*
The intervention group received Luxturna (1.5 x 1011 vg/eye in 0.3 mL) to each eye (on separate days).
The control group did not receive any treatment.
Primary endpoint: Change in bilateral multi-luminance mobility test (MLMT) score at Year 1 relative to baseline.‡
- Assessed participants’ ability to navigate a course with obstacles in varying low light conditions called Lux levels.1,2
- Before and 1 year following Luxturna treatment/no treatment.
- Sensitivity to light (via a full-field light sensitivity test, FST)
- The MLMT of the first treated eye
- Best-corrected visual acuity
- Exploratory endpoints: Visual fields and answering a visual function questionnaire.
After one year, the study was completed.
- Control patients could then receive Luxturna treatment (crossover/control patients).
*Patients included in the study had visual acuity of 20/60 or worse in both eyes and/or visual fields less than 20 degrees in any meridian; and an ability to perform multi-luminance mobility test within the light levels evaluated but unable to pass at the lowest level. Baseline testing randomisation was 2:1 intervention to control and participants were assigned to a group based on stratification for age and baseline primary endpoint performance. Study was fully enrolled in 2013; randomisation completed in 2014. All patients enrolled had a diagnosis of LCA associated with biallelic RPE65 mutations.1,2
†Intention to treat (ITT) population. One patient from each group withdrew before treatment. All followed control participants could crossover and receive Luxturna.
‡The MLMT test involved participants navigating a course with obstacles in various light (Lux) levels and is a proxy for functional vision. A score (MLMT Lux Score) was assigned based on navigation through the MLMT course at a lower light level.1,2
MLMT course image copyright of Spark Therapeutics.
The safety and efficacy of Luxturna in children aged up to 4 years or in patients ≥65 years old have not been established.
LCA, Leber congenital amaurosis; MLMT, multi-luminance mobility; VG, vector genomes.
Multi-luminance mobility test (MLMT)
Course navigation before and after Luxturna treatment
Baseline visit at 1 Lux (FAIL)
1-year visit after Luxturna administration at 1 Lux (PASS)
The camera used automatically adjusts the level and temperature of light that it captures. Because of this feature, there may be slight variations in hue when filming at low light levels (e.g. 1 Lux). Both videos were filmed in low‑light environments. 4 Lux is equivalent to a cloudless summer night with half moon or outdoor parking lot at night.
Note: Phase III trial participant MLMT videos (bilateral testing). This baseline passing level was 50 Lux and 1 year passing level was 1 Lux. Video is representative of clinical trial participants with clinically meaningful score change of 2 from baseline. Video source: Spark Therapeutics.
MLMT light levels with examples§
§NIST-calibrated, Extech model #EA33 light meter used to both provide light examples and set light levels for MLMT.
Adapted from Chung et al. 2017.4
NIST, National Institute of Standards and Technology.
Luxturna is a one-time transformational gene therapy that introduces a functioning RPE65 gene into the retina, restoring the visual cycle1,2
Measurable improvement as early as Day 30.1,2*
of patients benefitted from improved functional vision* and majority (72%) achieved maximum improvement5,6†
>100-fold improvement in low light sensitivity1,2‡
- Significantly improved total sum degrees and macular sensitivity1§
- No decline in mean change in best-corrected visual acuity (BCVA)1,2#
Improvements in vision outcomes sustained over 4 years of follow-up (Phase I follow-on study)7**
- 3 years for Phase III clinical trial patients1,5,6
Safety profiles determined and efficacy demonstrated across 3 clinical trials1,5,6
A total of 81 eyes tested in clinical trials1,5
*Measurable improvement was being able to navigate the MLMT course at the lowest luminance (Lux) level tested. Compared to baseline (Phase III study).
†Improvement of at least 1 light level from baseline for Phase III original Intervention Patients and Crossover patients at Year 1 following treatment with Luxturna.
‡Difference in FST of -2.11 log units ([-log10(cd.s/m2]) between Intervention (n=20) and Control Patients (n=9) at Year 1; p=0.0004.
§Goldmann III4e sum total degrees, monocular average over both eyes, p=0.006; Humphrey macular threshold, dB, monocular, averaged over both eyes; p<0.001.
#Holladay Scale measurements demonstrated a non-significant trend of improved VA (p=0.27). Lange Scale off-chart measurements demonstrated a significant improvement for Intervention Patients vs Control Patients (p=0.0047).
**Phase I follow-on study patients received the indicated dose of Luxturna to their untreated eye.
The safety profile of Luxturna has been demonstrated across 3 clinical trials3
- Luxturna safety was assessed in patients aged 4 to 44 years.1–3
- A total of 81 eyes were tested in clinical trials.1–3
- The most common adverse reactions (≥5% incidence) were related to the administration procedure (including serious adverse events <5% incidence)1,5
- The majority of adverse events reported were of mild to moderate severity, non-serious and transient in nature, and occurred during the initial year of post-administration follow-up.1,5
- Non-serious adverse reactions related to the drug itself consisted of transient asymptomatic subretinal precipitates.1,5
- Serious adverse reactions related to the procedure were increase in intraocular pressure associated with treatment for endophthalmitis (n=1/41), retinal disorder (loss of foveal function; n=1/41) and retinal detachment (n=1/41).1,5
- Patients received corticosteroids before and after Luxturna treatment to reduce the possibility of an immune response.1
Common adverse reactions with Luxturna across 3 clinical trials1,5
Phase I follow-on + Phase III (n=40)
|Any ocular TEAE||27 (68)|
|Eye disorders||24 (60)|
|Chalazion (n=40)||1 (3)|
|Choroidal haemorrhage||1 (3)|
|Conjunctival cyst||1 (3)|
|Conjunctival hyperaemia*||1 (3)|
|Eye inflammation||3 (8)|
|Eye irritation||2 (5)|
|Eye pain||3 (8)|
|Eye pruritus||2 (5)|
|Eye swelling||1 (3)|
|Foreign body sensation in eyes||1 (3)|
|Macular degeneration†||1 (3)|
Phase I follow-on + Phase III (n=40)
|Macular hole||2 (5)|
|Ocular discomfort||1 (3)|
|Optic atrophy||1 (3)|
|Retinal deposits#||3 (8)|
|Retinal disorder**||1 (3)|
|Retinal haemorrhage||1 (3)|
|Retinal tear||3 (8)|
|Infections and infestations||1 (3)|
|Conjunctivitis viral||1 (3)|
|Injury, poisoning and procedural complications||1 (3)|
|Wound dehiscence||1 (3)|
|Intraocular pressure increased||1 (3)|
*Includes verbatim terms suture irritation and suture reaction
†Includes verbatim term macular thinning
§Includes verbatim terms epiretinal membrane and macular pucker
#Includes verbatim term subretinal precipitate
**Includes verbatim terms foveal thinning and loss of foveal function
TEAE, treatment-emergent adverse event.
A genetic diagnosis will help determine Luxturna eligibility
Patients are eligible for Luxturna if they have:
Confirmed biallelic RPE65 mutations
Sufficient viable retinal cells17
Genotype or refer your patients if they have:
Previous diagnosis of a rod-based dystrophy such as LCA or RP
OR if they have nyctalopia
Night blindness, inability to see in low light. Light-seeking behaviour in infants/young children.11
in combination with other symptoms including:
Uncontrolled/repetitive eye movements. Early onset in children <1 year of age.
Difficulty with dark adaptation8–10
Restricted visual fields8–10
ERG, electroretinography; LCA, Leber congenital amaurosis; RP, retinitis pigmentosa.
Connect your patient to a commissioned Luxturna Treatment Centre* in order to:
Confirm Luxturna eligibility (confirmation of biallelic RPE65 mutation, assessment of viable retinal cells and suitability for Luxturna surgery)
Measurement of the presence of sufficient viable retinal cells1,12
Plan and schedule the administration of Luxturna (if deemed appropriate)
Luxturna is only administered at certified UK commissioned Luxturna Treatment Centres*
*By physicians who have attended the European Medicines Agency mandated medical training programme.
Four centres across the UK have been commissioned by NHS England to administer Luxturna to eligible patients. These centres can be consulted to discuss your RPE65-mutation-associated IRD patients and their potential eligibility for Luxturna.
Please contact us for more information.
IRD, inherited retinal dystrophy; RPE, retinal pigment epithelium.
Indication: Luxturna is indicated 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.1
- Luxturna SmPC, 2020.
- Russell S et al. Lancet 2017;390(10097):849–860.
- Mahabadi N, Al Khalili Y. Neuroanatomy, Retina. Available at: https://www.ncbi.nlm.nih.gov/books/NBK545310 (Accessed August 2020).
- Chung D et al. Clin Exp Ophthalmol 2018;46(3):247–259.
- Luxturna EMA Assessment Report. EMA/CHMP/700911/2018. 2018. Available at: https://www.ema.europa.eu/en/documents/assessment-report/luxturna-epar-public-assessment-report_en.pdf (Accessed August 2020).
- Maguire AM et al. Ophthalmology 2019;126(9);1273–1285.
- Data on file_5. Novartis Luxturna Core Data Sheet (CDS). Version 1. 2019.
- Chung DC et al. Am J Ophthalmol 2019;199:58–70.
- Sahel JA et al. Cold Spring Harb Perspect Med 2015;5(2):a017111.
- Fahim AT et al. Nonsyndromic Retinitis Pigmentosa Overview. 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1417/ (Accessed August 2020).
- Di Iorio V et al. Genes 2017;8:280–297.
- Thompson D et al. Invest Ophthalmol Vis Sci 2000;41:4293–4299.