Prescribing information

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  • IRDs are a major cause of familial blindness worldwide and are associated with an inherited gene mutation affecting the function of the retina.2,3     
    • The IRD phenotype retinitis pigmentosa is the most common IRD,4 with 1 in 3000–1 in 7000 people living with this disease.2
  • IRDs differ in onset, severity and progression of the diseases2     
    • IRDs are characterised by the progressive deterioration of the rods and cones.2
    • There are >270 genes associated with IRDs.3
  • Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) both have subtypes related to pathogenic variants in RPE65.5

Chart showing candidate genes for inherited retinal dystrophy phenotypes.

  • Other IRD phenotypes include: achromatopsia, choroideremia, Stargardt disease, Best disease, Sorsby fundus dystrophy, Usher syndrome, Bardet-Biedl syndrome.2,6
  • The majority of patients with an RPE65-mutation-associated IRD have vision impairment in early childhood.5  
    • If untreated, patients usually progress to near-total blindness.5,7

Gene

  • Retinal pigment epithelium-specific protein 65-kDa (RPE65) gene encodes the RPE65 protein.1     
    • RPE65 is an all-trans-retinal isomerase. This key enzyme is expressed in the retinal pigment epithelium (RPE) and is responsible for regeneration of 11-cis-retinal in the visual cycle.1
  • Individuals with biallelic mutations in RPE65 may experience a reduction or absence in the RPE65 enzyme activity.1     
    • This leads to build-up of toxic precursors and damage to RPE cells, loss of photoreceptors and eventually complete blindness.1

 

Diagram demonstrating a disrupted visual cycle which can lead to various vision deficits.

Estimated prevalence of RPE65-mutation-associated IRDs

  • RPE65-mutation-associated IRD can be diagnosed as:     
    • Leber congenital amaurosis (LCA)/early-onset retinitis pigmentosa – 2–3:100,000 births (RPE65 mutations: 3–16% of all LCA).11     
    • Retinitis pigmentosa (RP) – 1:300 – 1:5000 births (RPE65 mutations: 2–5 % of all non-syndromic autosomal recessive RP).10,12

Pie charts showing estimated prevalence of RPE65 mutation-associated inherited retinal dystrophies, Leber congenital amaurosis and Retinitis pigmentosa.

 

Clinical signs and symptoms

 Chart showing the hallmark of an RPE65 mutation-associated inherited retinal dystrophy.

The hallmark of an RPE65-mutation-associated IRD (RPE65-IRD) is an inability to see in low-light conditions (night blindness, nyctalopia).5

 

 

RPE65 mutation-associated IRDs have overlapping signs and symptoms with other IRD phenotypes.15 

 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

> Light-seeking behaviour in children15

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Difficulty with dark adaptation2,5,11

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Nystagmus15–17

  • Uncontrolled/repetitive eye movements.
  • Early onset in children (common aspect of a rod-cone dystrophy).

 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Loss of visual acuity2,4,5

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Reduced colour vision2,5,16 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Reduced/undetectable ERG2,5,11

 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Lack of fundus autofluorescence2,5,16 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Failure to fix and follow15
In infants

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Restricted visual fields2,5,16

  • Patients may report that they have “tunnel vision”.
  • Annual rate of decline of 2% to 12% for V4e of the Goldmann perimeter ranges.
  • Varies among gene-specific subtypes.
  • Young patients may bump into things in low light

 

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Retinal degeneration5,9

  • Reduced retinal thickness
  • Loss of outer segment/outer nuclear layer

Chart showing the overlapping signs and symptoms of RPE65 mutation-associated inherited retinal dystrophies.

Fundus abnormalities2,5,16†

Pigmentary changes, retinal atrophy, vessel attenuation, optic nerve pallor

 

This image was originally published in the Retina Image Bank. David Callan, MD. Retinitis Pigmentosa. Retina Image Bank. 2014; 17341.

© The American Society of Retina Specialists.

 

Understanding the condition: See what they see.

 

 

400 Lux

 

250 Lux

 

125 Lux

 
 

50 Lux

 

10 Lux

 

4 Lux

 

 

The videos depict a mother walking with her son (Alex) who has an RPE65-IRD. “Alex cam” shows what Alex sees in various light (Lux) levels. “Mum cam” shows what Alex's mum sees at the same Lux level.

Alex and his mother are actors . The videos were developed by Novartis in collaboration with FundamentalVR. The representation of Alex’s vision is based upon the natural history study of patients with RPE65-mediated IRD and Phase III clinical trial. This has been confirmed by IRD experts to demonstrate an accurate representation of a real RPE65-mediated IRD patient.

ERG, electroretinography.

IRDs have overlapping signs and symptoms: The only way to fully diagnose an IRD is a genetic test.

 

Now that there is an approved gene therapy,1,7 an early and complete diagnosis of an IRD is more important than ever.

 

Images to help describe the features of genetic testing, the only way to fully diagnose an inherited retinal dystrophy.

>270 genes are associated with IRDs and with multiple phenotypes.3,4

 

 Images to help describe the features of genetic testing, the only way to fully diagnose an inherited retinal dystrophy.

Genetic tests can improve the accuracy of diagnoses and prognoses.17

 
 

 Images to help describe the features of genetic testing, the only way to fully diagnose an inherited retinal dystrophy.

Establishing a complete diagnosis offers patients more information about their IRD.    

 

 Images to help describe the features of genetic testing, the only way to fully diagnose an inherited retinal dystrophy.

of IRD patients are interested in having a genetic diagnosis for their disease.7*  

 
 

 

Identifying patients earlier with genetic testing can17:

Images to reinforce three key messages that gaining more knowledge is beneficial for patients.

Address uncertainty

Images to reinforce three key messages that gaining more knowledge is beneficial for patients.

Permit early intervention

Images to reinforce three key messages that gaining more knowledge is beneficial for patients.

Improve decision-making and management

 

Images to reinforce three key messages that gaining more knowledge is beneficial for patients.

Provide insight into prognosis

 

 

*In a survey of IRD patients.7

 

Click here to know more about genetic testing and referring for a genetic test

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

 

References     

  1. Luxturna SmPC, 2020.     
  2. Sahel JA et al. Cold Spring Harb Perspect Biol 2015;5(2):a017111.     
  3. RetNet: Summaries. 2019. Available at: https://sph.uth.edu/retnet/sum-dis.htm (Accessed August 2020).     
  4. Verbakel SK et al. Prog Retin Eye Res 2018;66:157–186.     
  5. Chung DC et al. Am J Opthalmol 2019;199:58–70.     
  6. Nash BM et al. Trans Pediatr 2015;4(2):139–163.     
  7. Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations. Highly specialised technologies guidance [HST11]. Available at: https://www.nice.org.uk/guidance/hst11/chapter/2-The-condition (Accessed August 2020).     
  8. Palczewski K. Invest Opthalmol Vis Sci 201;55(10):6651–6672.     
  9. Russell S et al. Lancet 2017;390(10097):849–860.     
  10. Orphanet. 2019. Available at: www.orpha.net (Accessed August 2020).     
  11. Fahim AT et al. Nonsyndromic Retinitis Pigmentosa Overview. 2000. https://ncbi.nlm.nih.gov/books/NBK1417/ (Accessed August 2020).     
  12. Weleber RG et al. Leber Congenital Amaurosis. 2004. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20301475/ (Accessed August 2020).
  13. Data on file. Spark Therapeutics.     
  14. Astuti GDN et al. Genes 2018; 9:21.     
  15. Henderson R. Paediatrics and Child Health 2020;30:19–27.     
  16. Di Iorio V et al. Genes 2017;8:280–297.     
  17. American Academy of Ophthalmology®, IRD Clinical Statement. 2016. Available at: https://www.aao.org/clinical-statement/recommendations-on-clinical-assessment-of-patients (Accessed August 2020).
LUX20-C005a October 2020.
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