EMA proposes waiving comparative efficacy studies for certain biosimilars
The European Medicines Agency (EMA) is proposing to waive comparative efficacy studies (CES) for biosimilars with a straightforward mechanism of action (MOA), such as monoclonal antibodies and recombinant proteins, to reduce the need for human studies in comparing a biosimilar medicine under development with the reference product.EMA published this proposal in a new concept paper published on 25 January, explaining that “when the biosimilar demonstrates a high degree of similarity to the RMP [Reference Medicinal Product] at the analytical and functional level, it may be possible to justify the omission of dedicated CES [clinical efficacy studies].”
EMA said that “with growing knowledge and the increasing possibilities of analytical and functional characterisation, revisiting the need for clinical efficacy trials for biosimilars (especially recombinant proteins and mAbs) is considered the next important step in order to keep the Biosimilar pathway attractive for developers and, at the same time, guarantee future access to safe and efficacious biologics for European patients.”
A forthcoming reflection paper will explore how “well-defined analytical/functional (quality) data can be predictive for the clinical outcome.”
Currently, sponsors of biosimilar products are required to submit in vitro and in vivo non-clinical data comparability data and comparative pharmacokinetic, pharmacodynamic, safety, and clinical efficacy data to support their applications.
Yet advances made in analytical sciences and “extensive” regulatory experience have prompted a reevaluation of whether in vivo non-clinical data, and for less complex biologicals with a “straightforward mechanism of action” the need for dedicated clinical efficacy and safety data.
The paper states that “currently, the need for Comparative Efficacy Studies (CES) is increasingly questioned in general.”
EMA said that the biosimilar regulatory framework is changing towards tailored development starting from smaller and “simpler” biologics, such as recombinant Granulocyte-Colony Stimulating Factor (rG-CSF), insulins or somatropin where comparative clinical efficacy trials is no longer required.
EMA cited a study led by Nadine Kirsch-Stafan of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, in Langen, Germany, which questioned the usefulness of comparative efficacy studies in regulatory decision-making when approving biosimilar mAbs and fusion proteins; the study was published in the 13 October 2023 issue of BioDrugs. The study analyzed marketing authorizations applications (MAAs) of 33 mAbs and three fusion proteins submitted to EMA from July 2012 and November 2022.
EMA recently concluded a pilot program to see whether tailored advice to sponsors earlier in the biosimilars development process could help EMA decide whether to waive clinical efficacy and safety trials in certain cases. Sponsors said they appreciated the feedback, yet the lack of mature quality data hindered the agency’s ability to provide scientific advice. (RELATED: EMA shares lessons learned from biosimilars pilot, Regulatory Focus 19 October 2021)
The deadline to comment is 30 April. After receiving the comments, EMA will draft a reflection paper that will be open to comment for six months.
Concept paper
