OBJECTIVES: Understand how the three major European HTA agencies have reviewed new Cell and Gene therapies (C&GT). HTA bodies dislike uncertainty and this is amplified for new C&GTs coming to market. We carried out this review to understand whether these products should be reviewed like other non-C&GT products.

METHODS: We first reviewed which C&GTs were approved, then we identified market availability in France, Germany and UK (NICE). Decisions by the three HTA agencies were reviewed.

RESULTS: We identified 20 C&GT which had been approved in Europe; 16 were on the market in France, 18 in Germany, and 15 in the UK. The most frequent comments from the HTA agencies were related to the uncertainty of long-term data, especially the curative fraction, trial design (eg single-arm trial), and lack of QOL data. Not all treatments were orphan drugs (or reviewed by NICE via HST (Highly Specialised Technologies ie ultra-orphan). Only 5 drugs had been reviewed via HST in England, and of those 5, four had also used the ultra-orphan route in Scotland. In France, most products obtained an ASMR 3 or higher ; in the economic dossiers submitted, it was often noted that there were extrapolation issues. In Germany, many products achieved a ‘not quantifiable’ benefit rating, with some products requiring additional data collection. In Germany, in many cases, issues are mostly deferred until the orphan threshold of EURO30m is exceeded and a full dossier needs to be submitted.

CONCLUSIONS: There is a mismatch between the inherent promise of C&GTs and HTA agency appraisals, which are adverse to uncertainty. Given the cost of these products, it will remain challenging for C&GTs to obtain a favourable HTA review in cost-effectiveness markets. Therefore, HTA approaches for these products need to be re-evaluated, or trials need to be continued for longer to obtain additional data.