Abstract
Blastoferon®, in the following referred to as the test product, is a pharmaceutical
product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar
to the innovator interferon beta la product (referred to as the reference product).
Pharmacokinetics and pharmacodynamics assays are critically relevant to demonstrate
similarity between biopharma-ceuticals. The aims of the present study were to investigate
the bioavailability (BA) of the test product (either absolute or relative to the innovator
product) and to compare the extent of increase of neopterin concentration following
administration of either product. Two studies were performed: initially, an absolute
BA assay with i.V. and s.c. injection of test product to 12 healthy subjects. Second,
a formal relative BA study with s.c. injections of 88 μg of both products to 24 healthy
volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn
at different intervals after injection. Interferon beta (IFNB) concentrations were
determined by ELISA. In the absolute BA study, a single s.c. dose of 44 μg of the
test product resulted in a median bioavailable fraction of 29%, a median Tmax of 4 h (4–6) and a Cmax of 3.69 (3.27–4.41) IU · ml−1.
In the relative BA study, values for the test product were: median Tmax of 3 h (2–18), Cmax of 5.39 (4.99–6.31) IU · ml−1, AUC(0–72) of 142.86 (134.16–190.15) IU 9 h ml1 and AUC(0–infinity) of 190.95 (174.23–303.13) IU 0 h ml−1. The corresponding values for the innovator product were: Tmax of 3h (l-24),Cmax of 4.44 (4.12–5.40) IU I ml−1, AUC(0–72) of 128.77 (121.18–170.92) IU 7 h ml−1 and AUC(0-infinity) of 192.61 (183.04–286.46) IU 8 h h ml−1. The Alicia ratio was 111% (CI 90%: 106–116), the AUC(0-infinity) was 99% (CI 90%: 92–107) and the Cmax ratio was 121% (CI 90%: 112–131). IFNBla increased neopterin levels in both studies.
Both products induced side-effects commonly reported for IFN with no serious adverse
events. This study presents pharmacokinetics parameters of the test product and demonstrates
similar bioavailability of IFNBla for both pharmaceutical products.
Key words
Blastoferon®, bioequivalence, pharmacokinetics - CAS 220581-49-7 - Immunomodulators
- Interferon beta la
