Presentation (CTI)

OBJECTIVES: To examine how three European HTA bodies with distinct decision archetypes- cost-effectiveness-driven (NICE, UK), clinical-benefit-driven (HAS, France) and innovation/managed-entry-driven (AIFA, Italy) - translate the level of unmet need into added-value and access decisions for gene therapies sharing uncertain evidence bases.
METHODS: Three gene therapies spanning an unmet-need gradient were selected: Upstaza® (aromatic L-amino acid decarboxylase deficiency; high need), Casgevy® (transfusion-dependent β-thalassaemia; moderate need) and Hemgenix® (haemophilia B; low need). Need tiers were determined by evaluating the absence or limitations of disease-modifying treatments and the severity of residual burden relative to therapy. For each appraisal at NICE, HAS and AIFA, native ratings, access mechanisms, archetype-specific levers, comparator and endpoint acceptance, indirect-comparison outcomes and cited uncertainties were extracted from appraisal documents and AIFA's reimbursement determinations.
RESULTS: All three bodies relied on single-arm pivotal evidence yet responded to the need gradient through native levers. For Upstaza® (high need), each applied its most permissive stance: NICE routine commissioning, HAS ASMR III, and AIFA full innovativeness. For Casgevy® (moderate need), conditionality increased - NICE managed access with mandated data collection, HAS ASMR IV with age restriction, and AIFA full innovativeness layered with price discount, registry and time-limited agreement. For Hemgenix® (low need), evidence-generation demands peaked: NICE restricted managed access, HAS rejected the indirect comparison while holding ASMR at IV, and AIFA downgraded to conditional innovativeness. Evidence-quality concerns featured in all appraisals but did not reverse the directional pattern.
CONCLUSIONS: All three archetypes coupled greater evidentiary tolerance to higher unmet need, each through a different lever - conditionality (NICE), ASMR (HAS), innovativeness (AIFA). Unmet need is therefore decisive rather than contextual in how immature evidence is judged. Value narratives that clearly establish the level of need - where it is genuinely high - are best placed to unlock this flexibility, market-specifically. The need-agnostic EU JCA may sharpen this divergence.