Presentation (CTI)

OBJECTIVES: Current evidence requirements for orphan drugs (ODs) with conditional marketing authorization (CMA) vary across European HTA bodies. With mandatory Joint Clinical Assessment (JCA) implementation in 2025 introducing unified evidence standards, understanding how ODs with recent CMA perform against national HTA requirements should help to identify potential systemic challenges. This study analyzes relevant reimbursement decisions across major European HTA bodies to evaluate alignment with proposed JCA methods.
METHODS: Systematic analysis of HTAs for 17 ODs with CMA (9 in 2022, 8 in 2023). Data was extracted from official HTA body websites. Assessment outcomes were categorized as positive (reimbursed), restricted, or negative (insufficient benefit). Key JCA requirements considered: non-RCT risk of bias evaluation, surrogate outcome validation, network evidence assessment, and methodology for non-randomized comparisons. Analysis included evaluation of decision rationales and evidence requirements against JCA criteria.
RESULTS: There were consistent patterns across HTA bodies, with negative or restricted recommendations driven by evidence limitations that would also be critical under JCA requirements: lack of RCTs (76%), insufficient comparative data (82%), and inadequate follow-up periods (65%). Among 2022 approvals (n=9), evidence limitations led NICE to issue positive recommendations for only 5 products (56%), all required managed access or commercial arrangements to address evidence gaps. Similar evidence limitations led HAS to grant insufficient ratings in 22% of cases or receive no dossier submission, while G-BA could not quantify additional benefit in 44% of cases due to methodological limitations that align with proposed JCA criteria.
CONCLUSIONS: Analysis reveals significant challenges in demonstrating value of orphan CMAs under current HTA frameworks, with many products receiving restricted recommendations or requiring additional evidence generation. The upcoming JCA implementation is likely to amplify current value demonstration challenges faced by ODs with CMA due to its emphasis on comparative effectiveness. Further research is needed to determine the value of such medicines under JCA.