Presentation (CTI)

OBJECTIVES: Huntington's disease (HD) is a fatal neurodegenerative condition caused by a single gene mutation. Carriers can be genetically identified decades before symptoms appear, typically in their 20s-30s, with symptom onset usually in the 40s-50s. Emerging gene therapy has shown evidence of delaying disease progression in early-symptomatic patients; however, prescriber and patient demand to treat earlier is expected to be strong, despite clinical benefit only becoming observable 10-20+ years later. This research assesses EU5 payer willingness to reimburse a one-time gene therapy for genetically confirmed but pre-symptomatic HD patients and characterises required evidence and acceptable risk-sharing arrangements.
METHODS: A structured survey was conducted with N=15 ex-payer experts across EU5 markets (N=3 per market). Respondents indicated reimbursement willingness, required evidence (surrogate biomarkers, extrapolation from early symptomatic trial data, long-term registries), appropriateness of existing HTA frameworks (including discount rates) for preventative gene therapies, and preferred risk-sharing structures.
RESULTS: Reimbursement appetite split between 'yes in principle' (60%), 'possibly with conditions' (20%), and 'unlikely/no' (20%). Of those expecting reimbursement possible, 41% accepted surrogate biomarkers, 31% preferred extrapolation from early symptomatic data, 26% could not recommend evidence given disease complexity, and 31% required long-term registries to confirm durability. Most (67%) deemed current HTA frameworks inadequate for preventative gene therapies, calling for natural-history modelling and periodic re-evaluation. Discount rates were judged appropriate by 80%; 20% favoured lower rates for preventative therapies. Preferred contracting was outcomes-based with long follow-up (33%) and coverage-with-evidence-development (33%).
CONCLUSIONS: EU5 payers acknowledge HD gene therapy's transformative potential but require robust natural-history evidence, long-term registries, and outcomes-based contracting to bridge the pre-symptomatic evidence gap. Manufacturers should anticipate conditional reimbursement, with limited payer appetite for discount-rate adjustment despite the long horizon.