Presentation (CTI)

OBJECTIVES: Clinical evidence and efficacy are central to Health Technology Assessment (HTA). For advanced therapy medicinal products (ATMPs), however, small patient populations and limited data frequently challenge traditional evidence standards. In such a case, contextual factors, including disease severity and unmet medical needs, could gain importance. The EU HTA framework lacks mechanisms for incorporating these factors, raising concerns about its impact on ATMP evaluations. This study aimed to review the evidence supporting ATMPs and analyze their assessment outcomes by the French HTA agency (HAS) depending on disease contexts, together with implications for the evolving EU HTA framework.
METHODS: ATMPs with HTA reports in France were identified via the NaviHTA database. Evidence was assessed by study design, presence of comparators, and outcome relevance. HAS benefit ratings were analyzed relative to disease characteristics, including patient age, disease severity, available treatment options, and level of unmet need.
RESULTS: Among 29 ATMPs evaluated, 86% relied on non-randomized studies; 59% lacked comparative data, and only 17% included a relevant comparator. In 83% of cases, efficacy was not demonstrated using validated surrogate or hard clinical endpoints. No significant impact on mortality and patient-reported outcomes was observed in 86% and 93% of cases, respectively. Nearly all indications (97%) were for life-threatening conditions. Despite 79% having existing therapeutic alternatives, unmet needs were rated moderate to high in all cases. Ultimately, 83% of ATMPs received reimbursement in France, and 63% demonstrated at least minor clinical benefit. Pediatric indications and higher unmet needs correlated with higher improvement in benefit (ASMR) ratings.
CONCLUSIONS: Despite limited and low-quality clinical evidence, contextual factors often support reimbursement of ATMPs in France. A decontextualized EU HTA approach may increase negative outcomes and restrict patient access, underlining the need for flexibility or tailored pathways for ATMPs.