Presentation (CTI)

OBJECTIVES: RWE is increasingly used in HTAs to inform pricing and reimbursement (P&R) decisions for rare diseases, where trial data are limited. This review assessed its role in HTA decision making for rare disease therapies across the UK, Germany, France, Italy, and Spain (EU4 + UK).
METHODS: A targeted literature review identified HTA submissions across the EU4 + UK countries, for therapies designated as orphan drug by the European Medicines Agency, which incorporated RWE for P&R decisions. Review included published HTA appraisals and peer-reviewed PubMed articles from 2014 to 2025.
RESULTS: Sixteen rare disease therapies received reimbursement approval across EU4 + UK, including NICE (UK, n=8), HAS (France, n=6), G-BA/IQWiG (Germany, n=6), AIFA (Italy, n=5), and AEMPS/AETS (Spain, n=7). Neurological disorders were the most common therapeutic indications (n=7). Gene therapies represented the largest proportion (n=4), followed by enzyme replacement therapies (n=3), and antisense oligonucleotides (n=3). Onasemnogene abeparvovec and Elosulfase alfa were reimbursed in all five markets. Since 2019, RWE use has increased to address clinical and economic uncertainties, particularly for gene therapies. Key RWE sources included natural history studies (n=7), external comparators/controls (n=6), registries, post-marketing surveillance (n=5), and early access programs (n=3), supporting assessments of effectiveness, safety, and cost-effectiveness. In 44% of cases, RWE was pivotal for full or positive reimbursement; in others, it supported conditional reimbursement or restricted access. NICE and AEMPS showed greater acceptance of RWE, incorporating natural history data and external comparators. AIFA leveraged RWE via outcome-based agreements and registries. HAS used RWE for re-evaluations or broad reimbursement, while G-BA remained more restrictive, accepting RWE mainly for ultra-rare conditions.
CONCLUSIONS: HTA bodies have primarily accepted RWE to provide external comparators or to supplement clinical effectiveness data in rare disease therapies, though acceptance remains variable across agencies and may become more standardized under the EU Joint Clinical Assessment (EU-JCA).