OBJECTIVES: In recent years there has been a surge in the development of combination therapies, the ‘novel-novel’ aspect of which has introduced new challenges for payers and Health Technology Assessment (HTA) bodies looking to assess the value of the individual treatment components. The objective of this study is to assess existing HTA frameworks in key EU markets in the context of ‘novel-novel’ combination therapies to understand the compatibility of today’s system to this evolving paradigm, and identify challenges associated with the evaluation of the added-benefit of combination therapies.

METHODS: Qualitative in-depth 60-minute interviews with payers within the EU5 markets and industrial expert stakeholders (n=10), was complemented by a pragmatic literature review of published HTA reports for ‘novel-novel’ combination therapies.

RESULTS: The dual element of ‘novel-novel’ combinations often introduce additional complexity to HTA evaluations largely due to three reasons. Firstly, the clinical value for novel-novel combination therapies may not be fairly captured during HTA evaluations, particularly in disease area with high residual unmet needs, or where combination therapies are necessary to break resistance barriers. Secondly, there remains a suboptimal understanding of the underlying value of individual components and the potential synergistic increment from combining them. Lastly, pricing fairly between novel components remains challenging, with “back-bone” agents often benefit from a lower pricing pressure during payer negotiations due to first-mover advantage, despite their intended combined use.

CONCLUSIONS: In the short-term, clinical development and market access tactics should be planned to optimize the value demonstration of novel-novel combination therapies. In the long-term, increased collaborations between manufacturers and HTA bodies are needed to calibrate the evaluation framework in a dynamic manner in order to fairly assess the value of each novel asset within a combination therapy.