Epoetin Biosimilars in Europe: Five Years On...Adv Ther (2013) 30(1):28–40. DOI 10.1007/s12325-012-0072-2 REVIEW Epoetin Biosimilars in Europe: Five Years On Ashraf Mikhail · Mourad
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biosimilar versions of the same reference product.
If clinicians wish to ensure that a given patient
receives a specific biologic or biosimilar, they should
prescribe by brand name to prevent unintentional
substitution by pharmacists and allow for effective
pharmacovigilance. This approach has been highly
recommended in guidelines and legislation released
in different EU countries, advocating the avoidance
of automatic substitution [10].
In recognition of the need for special
requirements for effective pharmacovigilance
for biologics, new pharmacovigilance legislation
came into effect across the EU in July 2012 [39].
This legislation requires that for all adverse
drug reaction reports, all appropriate measures
should be taken to identify the brand name and
batch number of the product concerned. Recent
EMA guidance has reaffirmed the fundamental
differences between biosimilar and generic
medicines, and acknowledged the importance
of the patient and physician in prescribing/
switching decisions, recommending that
“for questions related to switching from one
biological medicine to another, patients should
speak to their doctor and pharmacist” [40].
CONCLUSION
Although considered therapeutically equivalent
by the EMA, the registration studies for HX575
and SB309 reviewed here suggest that differences
in their PK and dosing properties exist. The CHMP
strongly recommends that each confirmatory
study for biosimilar epoetins has two co-primary
endpoints – change in hemoglobin and change in
average dose – and that a biosimilar is approved
based on therapeutic equivalence on both primary
endpoints, assessed by CIs for between-group
differences that lie within pre-specified margins.
Such co-primary endpoints appear to have not
been included when some biosimilar studies
were undertaken. As differences do exist between
biosimilars, both in terms of their means of
manufacturing and glycosylation profiles, long-
term safety and tolerability should continue to be
monitored. Automatic substitution of biological
medicines is not encouraged and clinicians
should be fully involved when a switch between
originator products and biosimilars is considered.
Additionally, appropriate pharmacovigilance
measures should be put in place to ensure that
adverse events are attributed to the responsible
biological medicine.
ACKNOWLEDGMENTS
The preparation of this manuscript and article
processing charges were supported by a grant
from Amgen Inc. The authors would like to
acknowledge the assistance of Mark Greener
and Julia Balfour, medical writers, and Springer
Healthcare Ltd in the preparation of this
manuscript. The authors are responsible for the
final version of the review. Dr. Mikhail is the
guarantor for this article, and takes responsibility
for the integrity of the work as a whole.
Conflict of interest. Ashraf Mikhail has
received consultancy fees from Amgen, Johnson
& Johnson, Takeda, and Lipoxen, and a research
grant from Roche UK. Mourad Farouk is an
employee of Amgen, producer of epoetin alfa
(Epogen) and darbepoetin alfa (Aranesp), and
holds Amgen stock and stock options.
Open Access. This article is distributed under
the terms of the Creative Commons Attribution
Noncommercial License which permits any non-
commercial use, distribution, and reproduction
in any medium, provided the original author(s)
and source are credited.
Adv Ther (2013) 30(1):28–40. 39
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