study programme of the original drugs, where the
focus is the comparison of clinically relevant efficacy
and safety profiles of two therapeutic regimens. In
clinical studies, pre-existing pharmacovigilance data
on the reference product help validate the safety data
obtained from biosimilar studies, and are compared
with historical data or in direct head-to-head
comparability studies. Therefore, bridging studies
correlating critical attributes of the antibody and
pharmacovigilance data are required to support the
use of biosimilars, irrespective of the source of the
drug. Also, not only should patient data in the market
be followed up over time (for example, safety data
collection after approval), but data on the quality of
the biosimilar should also be generated. Confidence
in biosimilars will thus depend on how transparent
this assessment is. Norway, Finland or Hungary). Data show that similar
immunogenicity and safety exist between the
biosimilar and the original infliximab, and these
results have resulted in some regulatory bodies in
the EU supporting interchangeability. 26,27
Data from an independent study sponsored by
the Norwegian government (NOR-SWITCH) designed
to assess the efficacy, safety and immunogenicity of
biosimilar Remsima have added to the real-world
evidence that supports switching patients from
reference infliximab to biosimilar infliximab. The
biosimilar was non-inferior to its reference product
in adult patients who had been switched to receive
treatment with the biosimilar for 54 weeks; all
participants had been on stable treatment with the
reference product for at least six months prior to
switching to the biosimilar. 28
Risks associated with switching
Development programmes of several biosimilars
have included studies in which the reference
product has been switched to the biosimilar and,
occasionally, back to the reference drug. Epoetin
(EPO) is a highly glycosylated protein that depends
on post-translational modification for its mechanism
of action and is one of the few therapeutic proteins
to induce severe immunogenicity reactions;
however, no serious adverse events based on
immunogenicity have been reported in regard to
switching from EPO reference products to biosimilars.
Results regarding use of infliximab have not
raised concerns either. Transition data from the
PLANETAS and PLANETRA extension studies showed
comparable rates of serious treatment-emergent
adverse events between the maintenance and
transition groups. The anti-drug antibody positivity
and hypersensitivity reactions during the second
year of both studies did not differ significantly
between patients exposed to the reference product
or biosimilar as compared with those who received
only the biosimilar over two years. 24,25 This view
is supported by the fact that switches between
these reference products and biosimilars have
been accepted in some EU Member States (Poland, Development timelines
It is the general perception that biosimilars can
progress from bench to shelves in a shorter period
of time than conventional biologics and small-
molecule drugs. The stages of comparative analysis,
process development, scale-up and validation, clinical
trials, and review and approval of the biosimilar by
regulatory agencies might in fact take 5–9 years, and
the main challenge is conducting long and expensive
studies, in particular because in many cases the study
designs are not sensitive enough to detect differences
between the reference product. 29 Another challenge
in terms of timelines for development concerns the
degree of protection conferred by patents for the
original biologics, which have a period of exclusivity
that varies per country once the agent receives
approval for commercialisation, during which
a biosimilar cannot be marketed.
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