OBJECTIVES: Antibody-drug conjugates (ADCs) combine targeted therapy and chemotherapy and are among the fastest growing anti-cancer drugs, with numerous pipeline trials propelling their growth. This review aims to identify trends in health technology assessment (HTA) submissions of ADCs to European regulatory bodies, highlighting the driving factors necessary for future submissions.

METHODS: HTA recommendations and conclusions from key markets such as the UK (National Institute of Health and Care Excellence [NICE]), the Netherlands (Zorginstituut Nederland [ZIN]), France (Haute Autorité de santé [HAS]) and Germany (Institute for Quality and Efficiency in Health Care [IQWiG]) were analyzed for eight European Medicines Agency (EMA)-approved ADCs.

RESULTS: In the UK, NICE has issued favorable recommendations for all eight approved ADCs, highlighting their ability to effectively delay disease progression within acceptable cost-effectiveness estimates. In the Netherlands, the ZIN categorized all ADCs as ‘expensive medicines’, due to their high cost. The ZIN cited uncertainties about long-term effects like overall survival and quality of life, recommending negotiation with manufacturers before reimbursement. The HAS issued favourable opinion for almost all ADCs with a Service Médical Rendu (SMR) ‘important’ status. However, most ADCs receive a moderate-to-minor improvement in actual benefit (Amélioration du Service Médical Rendu [ASMR] III/IV), primarily because the Transparency Committee expects a better toxicity and quality of life profile compared with existing treatments. In Germany, ADC submissions are increasingly being rated as having ‘no additional benefit’, apart from trastuzumab deruxtecan. This trend is likely driven by uncertainty regarding evidence provided by the manufacturer.

CONCLUSIONS: ADCs face divergent evaluations in Europe: the UK and France support their reimbursement, citing benefits and cost-effectiveness, while the Netherlands and Germany express concerns over high costs and uncertain long-term effects, advocating for cautious reimbursement and negotiation. Prospective HTA submissions of ADCs should anticipate rigorous evaluation of evidence and possible reassessment or renegotiation.