Presentation (CTI)

OBJECTIVES: Biomarker-based drug-therapies in oncology typically treat rare populations. Germany's AMNOG legislation grants automatic added-benefit status to drugs with formal orphan drug (OD) designation, recognizing the difficulty of generating comparative evidence and the frequent absence of therapeutic alternatives. This analysis compared added-benefit ratings between biomarker-based and non-biomarker-based oncology drug-therapies and examined why added benefit was not proven.
METHODS: This retrospective analysis covered 521 oncology dossiers assessed by IQWiG and/or G-BA from January 2011 to June 2026 (Cellbyte database). Outcomes were classified as added benefit confirmed (with degree) or not proven. For orphan drugs, whose added benefit is legally granted, submitted evidence was recorded as accepted, rejected, or absent. Price rebate impact was also assessed.
RESULTS: "No added benefit" was more frequent for biomarker-based assessments (42.2% vs 36.6%; 50.8% vs 46.6% excluding orphan-protected assessments). A "major" added benefit was 4.2-fold more common (2.9% vs 0.7%), and "considerable or better" benefit was higher (27.4% vs 22.9%). Orphan drug designation was granted less often to biomarker drug-therapies (16.5% vs 21.2%). Among orphan assessments whose legally granted benefit rested on "non-quantifiable added benefit", the evidence was rejected for 82.6% of biomarker drug-therapies (mean 626 patients/dossier) versus 70.5% of others (mean 1,984). Where evidence was accepted, orphan biomarker drugs incurred smaller price rebates than other orphans (−2.5% vs −9.8%).
CONCLUSIONS: Current AMNOG implementation does not address the evidence-generation challenges facing biomarker-based drug-therapies in oncology. Although these drugs are more likely to earn higher benefit ratings, they are less likely to have an added benefit confirmed—explained by OD designation being granted less often to biomarker drug-therapies and, where granted, by smaller populations facing higher evidentiary hurdles. Yet when evidence is accepted, rebates are substantially lower. The absence of an automatic benefit pathway for rare, biomarker-based drug-therapies lacking formal OD status conflicts with AMNOG's original patient-centered intent and warrants policy reconsideration.