OBJECTIVES The number of Advanced Therapy Medicinal Products (ATMPs) approved by the EMA has increased over the past 5 years. These products are associated with challenges in market access. This review aimed at assessing reimbursement decision-making drivers of recent ATMPs (stem cell and gene therapies) across Germany, France and the UK.

METHODS Recent Health Technology Assessments (HTAs) from the Federal Joint Committee (G-BA), the National Authority for Health (HAS) and the National Institute for Health and Care Excellence (NICE) on darvadstrocel (Alo), voretigene neparvovec (Lux), betibeglogene autotemcel (Zyn) and onasemnogene abeparvovec-xioi (Zol) were reviewed.

RESULTS In Germany, the G-BA recommended Alo and Zyn with non-quantifiable additional benefit (and in a specific populations for Alo), while Lux showed major additional benefit. Zol assessment was suspended in December 2020 upon sales >50 million euro and additional evidence requests. In France, the HAS recommended Alo, Zyn and Zol respectively with minor improvement (Alo) in clinical added benefit (CAB IV) or moderate improvement (CAB III) in some subpopulations while Lux was the only drug showing major improvement (CAB II) in the fully approved indication. Cost-effectiveness analyses (CEAs) were required due to the expected turnovers at 2 years, except for Alo. In the UK, the NICE did not recommend Alo as the clinical trial showed additional benefit only in 14% of people and the long-term benefits were unclear. CEAs were consequently highly uncertain to allow for plausible estimates. Lux is recommended in its approved indication given the good clinical trial evidence but only at the agreed discount.

CONCLUSIONS Reimbursement is depending on the effect size of benefit and durability of response and could be limited to some subpopulations and not the fully approved indication. Agreements are also in place for economic affordability.