Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

A risk benefit analysis of Biosimilars

Dr. Monika Fürlinger (Abschlußjahr: 2014)

Summary
Currently, over 650 new biological medicines and vaccines are being developed to treat more than 100 diseases, which demonstrates the importance of biologicals drugs. But biological medicinal products belong to the high price segment. Health care providers face a steep rise of pharmaceutical expenditure due to an ageing population and the increasing uptake of these expensive biological medicines, especially for treatment of cancer and autoimmune disorders.
Biosimilars are a copy version of an already authorized biological medicine. In contrast to small drug generics, biosimilars are not identical to their reference product, but due to the inherited complexity of biopharmaceuticals only similar in terms of quality characteristics. There are many expectations in biosimilars: they represent an option for cost saving for health care providers and an opportunity for the industry to balance the risks of the innovation pipeline. But the major benefit of biosimilars might be their potential to cover  unmet medical needs and allow a broader range of patient access tobetter treatment.
The risks of biosimilars are linked to their complex three-dimensional structure, which restrict to identically copy a biosimilar with its reference product. Small structural differences, a divergent glycosylation or sialysation pattern or alterations in the impurity profile may trigger unpredictable immunogenic reactions. The EU Commission was the first authority  who established the legal framework to limit the risks associated with biosimilars. Other nations including the US, have started to develop their own legal framework, thereof many  following the example of the EU legislation. But still more efforts will be needed to harmonize different approval approaches of biosimilars. Equally essential it will be to ensure post-marketing safety by the corresponding pharmacovigilance measures which allow a timely detection of any safety signal of a biosimilar. Again the strict EU pharmacovigilance regulations may be taken as guidance to ensure the safety of biosimilars during post-authorization. Justified concerns remain in regard to interchangeability and substitution as in most cases no clinical data on switching are available. Currently we face another wave of biosimilars, the advent of biosimilar monoclonal antibodies. These  molecules are even more complex proteins than the rather small proteins on which today’s experience is mainly based. The difference in the immunogenicity profile of two different  monoclonal antibodies may only be marginal but with severe consequence in terms of safety.
The current experience leaves justified questions if biosimilars will meet all the expectations. The near future will show how biosimilars of blockbuster monoclonal antibodies will change the treatment option for therapeutic areas such as oncology or rheumatology. There is huge potential to transform the current landscape of biological medicines similar as it happened  by the introduction of small molecule generics. Time will tell, if biosimilar copy the success story of generics.
Pages: 55