OBJECTIVES: To review health technology assessment (HTA) evaluation for gene therapies (GTs) in France, England, and Germany, and tackle the challenges posed by their unique features in the rapidly evolving landscape of GTs.

METHODS: GTs approved/withdrawn in the European Union (EU) by 16 June 2023 were identified from regulatory websites; available HTA reports were extracted from websites of the HTA bodies and analysed.

RESULTS: Fifteen GTs were authorized in the EU, with 4 of them withdrawn upon manufacturers’ request. In France, despite the criticized quality of evidence, all 10 currently authorized GTs were recommended with different levels of clinical (added) value (one withdrawn with negative opinion). Indication restriction was recommended for 5 GTs because of limited data on subpopulations, and a reassessment of most GTs requested because of short-term data. In England, all assessed GTs were reimbursed within their label indication (N=8) or restricted indication (N=2); 3 GTs were funded via the Cancer Drugs Fund while collecting long-term data, and financial schemes were agreed for most GTs to address cost-effectiveness issues. In Germany, 2 GTs were assessed under standard process with no proven added benefit (AB) because of inappropriate comparator use, 10 GTs benefitted from the orphan drug (OD) pathway, 2 OD-GTs showed a considerable AB, and 8 OD-GTs showed a non-quantifiable AB, among which 2 were reassessed after exceeding the revenue threshold (one ongoing assessment, one with no proven AB).

CONCLUSIONS: GTs were recommended with some variations between countries, within <11 months on average, leveraging managed entry agreement and/or indication restriction in France and England, and OD pathway in Germany. With GTs included in the first wave of EU joint clinical assessments, the possibility of implementing a GT-dedicated and streamlined framework and potential indirect implications of EU HTA regulation in England remain to be assessed.