The evidence required to obtain marketing authorisation for a biosimilar by the regulatory authority is not always the same as that required by the reimbursement authority. This can cause problems for biosimilars manufacturers when planning clinical trials in order to obtain both marketing and reimbursement approval.
Reimbursement authorities often require non-inferiority studies in order to substantiate the claim of similarity between the biosimilar and the originator biological.
This, however, is not always available, since EMA may allow extrapolation of data in some cases to another indication of the reference biological without an evaluation of the biosimilar in this new patient population.
An increasing number of countries demand evidence about the cost-effectiveness of a biosimilar via an economic evaluation.
The economic evaluation should relate the relative costs of the biosimilar and the current standard treatment to their relative effectiveness.
In most cases, this means that the cost-effectiveness of a biosimilar needs to be established in comparison to the reference biological. In other cases, biosimilars have been developed for older biologicals, for which second-generation originator biologicals are now marketed and have become the standard treatment, e.g. second-generation erythropoietins and second-generation G-CSFs.
This implies that the cost-effectiveness of the first-generation biosimilar needs to be determined relative to the second-generation originator biological.
Example: filgrastim for preventing febrile neutropenia has been marketed in the EU since 1991 and five filgrastim biosimilars have entered the market since 2008 for the same indication.
A long-acting pegylated form of filgrastim, pegfilgrastim, was registered by EMA in 2002. As pegfilgrastim has become the standard treatment, any economic evaluation of a filgrastim biosimilar should calculate its cost-effectiveness relative to pegfilgrastim. A filgrastim biosimilar may look less cost effective if compared to pegfilgrastim.
The problem is that registration authorities demand clinical trials that demonstrate efficacy in a structured setting. However, reimbursement authorities require data on the effectiveness of a biosimilar in a real-world setting. Registration authorities will accept surrogate endpoints, whereas reimbursement authorities want to see data about primary health outcomes such as mortality or quality of life. One way around this is to use health economic modelling approaches if there is evidence of the relationship between the surrogate endpoint and the health outcome.