Value Assessment and Quantitative Benefit-Risk Modelling of Biosimilar Infliximab for Crohn’s Disease

Abstract

Aim: Regulatory approval of biosimilars often depends on extrapolating evidence from one clinical indication to all of those of the originator biologic. We aimed to develop a quantitative benefit-risk analysis to assess whether the resulting increase in the uncertainty in the clinical performance of biosimilars (i.e. risk) may be countered by their lower pricing (benefit). Methods: A one-year decision-analytic model was developed for the biosimilar infliximab (Inflectra®) for Crohn's disease. The perspective was that of the NHS in the UK and costs were valued to 2015/16. A hypothetical cohort of biologic-naïve patients with moderate-to-severe Crohn's disease were simulated through the model. Immunogenicity to infliximab was a key modifier, influencing rates of non-response and infusion reactions. Net health benefit was estimated based on quality-adjusted life years (QALYs). A range of sensitivity analyses tested the robustness of the results and explored how the biosimilar price must respond to varying immunogenicity to remain the preferred option. Results: The base-case analysis predicted a positive incremental net health benefit of 0.04 (95% Central Range 0.00-0.09) favouring the biosimilar, based on 0.803 QALYs, and costs of £18,087 and £19,176 for biosimilar and originator, respectively. Two-way sensitivity analyses suggested that if 50% of patients developed antibodies, the value-based price of £410 per vial must be lower than that of the originator (£420), but remain higher than the actual market price (£378). Conclusions: The model supports the use of Inflecta® for Crohn's disease in the UK, and provides a framework for the quantitative evaluation of biosimilars in the context of health technology assessment. Value-based pricing using this methodology could protect health systems from the potential risks of biosimilars where they are untested in the approved populations. Key points for decision makers  The base-case analysis predicts a positive incremental net health benefit of 0.04 (95% Central Range 0.00-0.09) favouring the biosimilar and suggests that if 50% of patients developed antibodies, the value-based price would need to be below the originator but higher than the current market price.  The study presents a novel framework for the quantitative benefit-risk assessment of biosimilars, illustrated with biosimilar infliximab for Crohn's disease  The methods provide an explicit framework for balancing risks (the uncertainty in the efficacy and harms of biosimilars) against their benefits (cost advantages)

A health economic guide to market access of biosimilars

“…A biosimilar receives marketing authorization based on the totality of the evidence, although residual uncertainties related to the benefit-risk assessment may remain at this stage (as is the case with any medicine), which can be addressed through postmarketing pharmacovigilance [54]. This can be illustrated by a UK economic evaluation of biosimilar infliximab for Crohn's disease, which explored the impact of a hypothetical difference in the immunogenetic profile of reference and biosimilar infliximab on cost-effectiveness [55]. The use of biosimilar infliximab was supported by the base case analysis given that both reference and biosimilar infliximab generated 0.803 quality-adjusted life-years over a one-year time horizon, but biosimilar infliximab (healthcare costs of £18,087) was less expensive than reference infliximab (£19,176).…”