OBJECTIVES: A rare disease affects fewer than 1 in 2,000 people, and around 80% have a genetic cause. Gene therapies alter the genes inside human cells to prevent/treat disease, offering potential to address high unmet need in rare diseases by providing a therapy where there are sometimes limited or no treatment options. However, a high-price and inherent uncertainty in the long-term clinical efficacy and safety data, threaten the accessibility of these therapies and create challenges for health technology assessment (HTA) bodies in assessing their cost-effectiveness. This research aimed to analyze previous highly specialized technology (HST) appraisals by NICE, as a case study, to highlight the challenges associated with cost-effectiveness assessments of gene therapies for rare diseases.

METHODS: A targeted review of previous NICE HST appraisals of gene therapies was performed by one reviewer, using the summary of evidence made publicly available via the NICE website.

RESULTS: To date (May 2024), NICE has appraised eight gene therapies through the HST route; five single-dose therapies (Strimvelis; Luxturna; Zolgensma; Libmeldy; Upstaza), and three enzyme replacement therapies with long-term dosages (Strensiq; Lamzede; Kanuma). Single-dose therapies ranged in list price from £505,000 for Strimvelis to £3,010,451 for Upstaza, although the Patient Access Scheme remains confidential. The economic models used a Markov model structure within most submissions (7 of 8). Notably, all eight gene therapies received positive recommendation, despite many uncertainties highlighted during the HST evaluations, including long-term treatment effect, source of clinical evidence, health-related quality of life evidence, and carer disutility data.

CONCLUSIONS: This overview of prior NICE HST appraisals of gene therapies provides insight to the potential issues faced by all stakeholders involved in technology appraisals of these innovative treatments. It also demonstrates the array of products that “gene therapies” captures, the differences in acquisition prices, and variation in economic model structure and approach.