Consideration of Off-Label Therapies as Appropriate Comparator Therapy in Early Benefit Assessments in Germany Under the ALBVVG Legislation
Author(s)
Susanne Brückel, Master of science1, Wioletta Kotowa, MD2.
1Team Lead HTA & Value Demonstration, IGES Institut GmbH, Nuremberg, Germany, 2Director HTA & Value Demonstration, IGES Institut GmbH, Nuremberg, Germany.
1Team Lead HTA & Value Demonstration, IGES Institut GmbH, Nuremberg, Germany, 2Director HTA & Value Demonstration, IGES Institut GmbH, Nuremberg, Germany.
OBJECTIVES: The determination of the appropriate comparator therapy (ACT) by the Federal Joint Committee (G-BA) plays a crucial role in early benefit assessments (EBA) in Germany. The Drug Supply Shortage Control and Supply Improvement Act (ALBVVG) clarifies under which circumstances off-label therapies can be considered as ACT. This analysis examines how the ALBVVG is applied in G-BA decisions and under which conditions off-label therapies are accepted as ACT.
METHODS: Four EBA procedures from July 2023 to May 2025, in which off-label therapies were discussed as comparators, were exemplarily selected for analysis. The G-BA decisions regarding the choice of ACT were analyzed with a focus on the reasoning provided in the supporting documents.
RESULTS: The selected EBA procedures showed varying outcomes: For dupilumab (eosinophilic esophagitis), an established off-label therapy was considered appropriate based on evidence-based guidelines and extensive clinical experience. For midostaurin (systemic mastocytosis), avapritinib, cladribine, and imatinib were recognized as ACT despite not all being approved for the corresponding indication, acknowledging their established role in treatment algorithms. For lisocabtagene maraleucel (various B-cell lymphomas after prior therapy), off-label use was deemed appropriate, particularly considering the disease severity and limited therapeutic alternatives for these vulnerable patients. Conversely, for talazoparib (metastatic castration-resistant prostate carcinoma), the off-label use of abiraterone acetate with prednisone/prednisolone and enzalutamide was not recognized by the G-BA as ACT, as these therapies would not be routinely preferred over approved alternatives.
CONCLUSIONS: The ALBVVG has legally clarified the conditions under which off-label therapies can be considered as suitable comparators in EBA. However, there are no fixed criteria establishing when an off-label treatment is generally preferable to previously approved medicinal products in the same therapeutic area. Instead, decisions are made on a case-by-case basis, which are discussed in-depth in the poster presentation. This lack of clear guidelines poses challenges for pharmaceutical companies.
METHODS: Four EBA procedures from July 2023 to May 2025, in which off-label therapies were discussed as comparators, were exemplarily selected for analysis. The G-BA decisions regarding the choice of ACT were analyzed with a focus on the reasoning provided in the supporting documents.
RESULTS: The selected EBA procedures showed varying outcomes: For dupilumab (eosinophilic esophagitis), an established off-label therapy was considered appropriate based on evidence-based guidelines and extensive clinical experience. For midostaurin (systemic mastocytosis), avapritinib, cladribine, and imatinib were recognized as ACT despite not all being approved for the corresponding indication, acknowledging their established role in treatment algorithms. For lisocabtagene maraleucel (various B-cell lymphomas after prior therapy), off-label use was deemed appropriate, particularly considering the disease severity and limited therapeutic alternatives for these vulnerable patients. Conversely, for talazoparib (metastatic castration-resistant prostate carcinoma), the off-label use of abiraterone acetate with prednisone/prednisolone and enzalutamide was not recognized by the G-BA as ACT, as these therapies would not be routinely preferred over approved alternatives.
CONCLUSIONS: The ALBVVG has legally clarified the conditions under which off-label therapies can be considered as suitable comparators in EBA. However, there are no fixed criteria establishing when an off-label treatment is generally preferable to previously approved medicinal products in the same therapeutic area. Instead, decisions are made on a case-by-case basis, which are discussed in-depth in the poster presentation. This lack of clear guidelines poses challenges for pharmaceutical companies.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA90
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
No Additional Disease & Conditions/Specialized Treatment Areas