ORPHAN DRUGS, HTA UNCERTAINTY AND ACCESS INEQUALITIES: A COMPARATIVE ANALYSIS BETWEEN FRANCE AND GERMANY
Author(s)
Rahma Sellami, PharmD, MSc1, Marine Sivignon, PharmD2, Clement Francois, MSc, PhD1, Yosra Boukhris, PharmD3, Nicolas Virely, PharmD,MSc1, Loris Blasco, PharmD, MSc4, Pol-Antoine Hamon, PharmD4.
1Inizio Ignite Putnam, Paris, France, 2Inizio Ignite Putnam, Lyon, France, 3Inizio Ignite Putnam, Tunis, Tunisia, 4LEEM, Paris, France.
1Inizio Ignite Putnam, Paris, France, 2Inizio Ignite Putnam, Lyon, France, 3Inizio Ignite Putnam, Tunis, Tunisia, 4LEEM, Paris, France.
OBJECTIVES: Despite increasing efforts toward HTA convergence in Europe, substantial differences remain in how national agencies assess medicines for rare diseases. Orphan medicines frequently enter the market with greater evidentiary uncertainty than non-orphan products, raising questions about how different HTA frameworks manage these limits and unmet medical need. This study evaluated the contribution of orphan medicines to divergences in HTA outcomes between France and Germany.
METHODS: A comparative analysis was conducted on medicines receiving a first European Medicines Agency (EMA) marketing authorization between 2022 and 2025. Access status and HTA outcomes from the French National Authority for Health (HAS) and the German Federal Joint Committee (G-BA) were assessed. Orphan medicines were analyzed separately, and divergences between French and German assessments were explored qualitatively.
RESULTS: HTA comparison was possible for 103 products with a published HAS opinion, grouped into three categories: those with a more favorable assessment in France, a more favorable assessment in Germany, or broadly equivalent assessments. Orphan medicines were disproportionately represented among products favored by Germany, accounting for 22 of 34 cases (65%). Several orphan medicines received an ASMR V rating or an insufficient SMR in France while obtaining recognized added benefit in Germany. Key drivers of divergence included reliance on non-comparative evidence, small sample sizes, uncertainty regarding long-term outcomes, and differences in the assessment of unmet medical need and clinical uncertainty. These differences are partly explained by the German orphan drug framework, under which added benefit is presumed below a defined sales threshold. However, qualitative review also suggested systematic differences in the weighting of unmet need, acceptance of immature evidence, and interpretation of clinical uncertainty.
CONCLUSIONS: Orphan drugs account for nearly two-thirds of France-Germany HTA divergences, suggesting that differences in the management of uncertainty and unmet need remain a major source of variation despite increasing European HTA harmonization.
METHODS: A comparative analysis was conducted on medicines receiving a first European Medicines Agency (EMA) marketing authorization between 2022 and 2025. Access status and HTA outcomes from the French National Authority for Health (HAS) and the German Federal Joint Committee (G-BA) were assessed. Orphan medicines were analyzed separately, and divergences between French and German assessments were explored qualitatively.
RESULTS: HTA comparison was possible for 103 products with a published HAS opinion, grouped into three categories: those with a more favorable assessment in France, a more favorable assessment in Germany, or broadly equivalent assessments. Orphan medicines were disproportionately represented among products favored by Germany, accounting for 22 of 34 cases (65%). Several orphan medicines received an ASMR V rating or an insufficient SMR in France while obtaining recognized added benefit in Germany. Key drivers of divergence included reliance on non-comparative evidence, small sample sizes, uncertainty regarding long-term outcomes, and differences in the assessment of unmet medical need and clinical uncertainty. These differences are partly explained by the German orphan drug framework, under which added benefit is presumed below a defined sales threshold. However, qualitative review also suggested systematic differences in the weighting of unmet need, acceptance of immature evidence, and interpretation of clinical uncertainty.
CONCLUSIONS: Orphan drugs account for nearly two-thirds of France-Germany HTA divergences, suggesting that differences in the management of uncertainty and unmet need remain a major source of variation despite increasing European HTA harmonization.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HPR43
Topic
Epidemiology & Public Health, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Coverage with Evidence Development & Adaptive Pathways, Health Disparities & Equity, Pricing Policy & Schemes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas