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Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 8
March 26-27, 2018 | Orlando, USA
World Summit on
Healthcare & Hospital Management
&
International Conference & Exhibition on
Biologics and Biosimilars
I
n his book,“
The End of History?
”, published in the National
Interest in 1992, Fukuyama argues that the advent of
Western liberal democracy may signal the endpoint of
humanity’s sociocultural evolution and the final form of
human government. In the same vein, based on recent
development of sophisticated analytical methods and
evolution of regulatory guidance, one should discuss the
relevance of the current clinical development model for
biosimilars and raise the (long term) question: “Is it the
end of clinical trials in biosimilar development?” or more
realistically “could we in a not too distant future drastically
reduce the financial and operational burden of biosimilar
clinical trials?” It is well known that proteins have unique
structural organisation patterns and even those that are
chemically identical may have different biological effects
due to structural folding differences, without mentioning
the effect of post-translational modifications. However,
with the current exponential development of multiple
sophisticated analytical methods enabling comparability
assessment between originators and candidate biosimilars
both structurally (orthogonal methods) and functionally
(compound-dependent), considering the lack of sensitivity
of many clinical models to detect meaningful differences
between follow-on biologics and reference compounds, and
the recent evolution of regulators perspective on this matter,
the relevance of the current clinical development model can
legitimally be questioned. Even if this is not ready for prime
time, we observe through interaction with regulators trends
that are compatible with this possible long-term perspective,
namely: reliance on healthy volunteer PK/PD studies only to
support some biosimilar compounds registration (without
testing the candidate biosimilar in oncology patients),
wider acceptance by FDA/EMA of extrapolation from one
indication to all other approved indications of the reference
compound (e.g. infliximab), and agencies willingness if not
encouragement to test clinical biosimilarity in non-approved
indications of the originator compound! When one considers
the financial and operational burden of running pivotal
trials based on clinical endpoints (skeletal-related events)
in some indications (e.g. osteoporosis, metastatic proste
cancer), the likely acceptability of surrogate markers (BMD
in osteoporosis), one can predict biosimilars clinical trials
designs and endpoints are likely to significantly evolve
in the coming years. However, one important question
remains open, at least for immunogenic compounds
(e.g. adalimumab), namely the opportunity to predict
immunogenicity based on non-clinical models.
e:
xavierfrapaise@yahoo.comThe end of clinical trials in biosimilars development
Francois-Xavier Frapaise
Merck, France