Presentation (CTI)

OBJECTIVES: Gene therapy (GTx) has emerged as a promising approach for curing life-threatening diseases, but its high cost poses significant economic challenges. We reviewed the NICE submissions of GTx to analyse the Evidence Assessment Group critiques and highlight key focus areas for future submissions seeking NICE approval for GTx.
METHODS: GTx approved between 2021 and 2026 were sought through desk research. NICE website was searched to identify and retrieve the technology appraisals (TAs) of these GTx. Information extracted from included TAs comprised critiques across PICOS, clinical evidence, economic evidence, patient-reported outcomes, final recommendations, and funding considerations. Critiques were categorised to identify recurring methodological challenges.
RESULTS: Ten NICE TAs covering 10 GTx and 11 indications were included for analysis. The common PICOS-related concerns were limited and highly selected trial populations (n=7), comparator misalignment (n=4), lack of direct comparative evidence (n=10), uncertainty in indirect comparisons (n=7), and reliance on surrogate outcomes (n=6). Population-related critiques reported in 9 TAs were primarily on limited generalisability to NHS practice, as studies often enrolled younger, fitter patients while underrepresenting older, frailer individuals, women, and those with comorbidities. Clinical evidence-related concerns cited in 8 TAs were about single-arm or non-randomised studies, alongside issues related to small sample sizes, limited follow-up, and uncertainty in real-world effectiveness. Economic critiques frequently focused on survival extrapolation, resource-use assumptions, and sensitivity of cost-effectiveness estimates to long-term outcomes. Patient and caregiver evidence consistently highlighted substantial unmet need, although direct patient-reported outcomes were often limited. Funding barriers for seven gene therapies were addressed through managed access and pricing schemes. Of 11 indications, 8 received full NICE recommendations, and three were conditionally recommended under managed access, with none rejected.
CONCLUSIONS: NICE appraisals of gene therapies frequently highlighted uncertainties in clinical and economic evidence. Strengthening comparative, long-term, and patient-reported evidence may improve future reimbursement decisions.