Project Name: RPE65 Genetic screening Project (“Joint Working” or “JW”)

Project Summary:

Patients with IRDs suffer from a number of clinical manifestations and vision impairment due to an inherited gene mutation affecting the function of the retina.  Included within this patient cohort, deletion or absence of RPE65 gene is among a number of causative genetic mutations responsible for conditions such as Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA), which is accountable for progressive and complete sight loss.  Historic stratification of the known IRD cohort has been challenging due to the wide range of potential mutations occurring within a large number of genes.  Furthermore, access to specific genetic panels (tests), including RPE65, is limited due to differences in reimbursement across the UK – currently NHS Northern Ireland do not have equivalent testing reimbursement for suspected cases compared to England – resulting in identification of genetic cause and RPE65 involvement remaining largely unknown and in any event, not identified across the wider Northern Ireland patient population.

Historically, no treatment has been available to treat or manage the deterioration of vision due to genetic cause and as a result patients with IRDs have largely been solely managed with measures to support poor/low vision without access to disease modifying therapies. The result is poor visual outcomes and impairments to quality of life.

Luxturna® (verotigene neparvovec) 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.  Luxterna has already received NICE approval; this has been accepted in Northern Ireland).  It is expected that the prevalence of patients with confirmed bailletic RPE65 mutations in the UK to be 1.2% of RP/LCA population, which represents 86 patients affected by biallelic RPE65 mutation; within Northern Ireland this is expected to be 1-2 patients.

The aim of this JW is to screen the Inherited Retinal Disease (IRD) population of Northern Ireland to identify patients with biallelic RPE65-mutations.  From this cohort, patients will either be eligible for  treatment with Luxturna or will be further classified and considered for further investigation.

Planned Milestones:

Belfast Healthand Social Care NHS Trust table

Expected Benefits:

List of benefits to the Patients:

  • Improved awareness and clarification of molecular cause of patient’s visual impairment;

  • Potential for improved future treatment / management options for patients entered into further clinical studies; and

  • Improved potential for eligible patients to enter into NICE approved therapy giving rise to potential for improved vision and reduction of risk of vision loss.

List of benefits to the NHS:

  • Improved understanding of genetic mutations within the IRD population;

  • Potential identification of patients eligible for treatment;

  • Identification of new patient cohorts for further genetic clinical study;

  • Improved reputation of Ophthalmology and molecular genetics services for IRD patient management; and

  • Potential publication in outcomes of prospective screening.

List of benefits to Novartis:

  • Improved reputation for Novartis nationally and internationally;

  • Potential identification of patients eligible for treatment with NICE approved therapy; and

  • Improved partnership alignment with the JWP

Start Date and Duration: June-2022, 12 months from date of execution of contract.