Gene therapies constitute a new concept of transformative therapies, administered once in a lifetime. The value assessment of these innovative therapies constitutes a challenge for health technology assessment (HTA) bodies.

The HTA reports for all seven gene therapies that have to date been granted a market authorization in the European Union (EU) and/or the United States (US) were examined to understand the rationale behind their assessment outcomes and to explore the differences in value assessment across US, England, Scotland, France and Germany.

In England, Imlygic® was accepted for use with the manufacturer agreeing to the application of a discount to the list price under a patient access scheme (PAS), while Strimvelis® was recommended due to its cost–effectiveness estimate being considered as reasonable under the highly specialized technology (HST) evaluation. KYMRIAH® and Yescarta® were approved for use within the Cancer Drugs Fund (CDF) in England, conditionally, as long as managed access agreements are upheld.

In France, KYMRIAH®, Yescarta®, and Luxturna® were considered as having important actual clinical benefit. In France, GLYBERA® was considered to have ‘insufficient’ benefit due to its unsustainable and heterogeneous treatment effects.

In Germany, the extent of the added benefit of GLYBERA®, KYMRIAH®, and Yescarta® was evaluated as ‘non-quantifiable’ as the submitted evidence made reliable, comparative assessments difficult. In Germany, Imlygic® was assessed to have no added benefit due to the selection of inappropriate comparators.

In Scotland, KYMRIAH® was accepted for B-cell acute lymphoblastic leukemia treatment with a PAS, while Yescarta® and KYMRIAH® for diffuse large B-cell lymphoma were rejected due to unjustified cost–effectiveness estimates.

In the USA, KYMRIAH®, Yescarta®, Luxturna®, and Zolgensma® were evaluated as having substantial net health benefits, however, a high certainty of conclusion for the assessment of Zolgensma® was established. Although the limitations in pivotal studies resulted in substantial uncertainties regarding long-term treatment benefit, there was still a possibility for gene therapies to gain acceptance from HTA bodies. Most importantly, further evidence collection becomes the critical key, not only to reduce the uncertainty in reimbursement decisions, but also to increase the public’s confidence in the use of gene therapies.