Introduction
G-CSF
Mechanism of action
Indications
-
Reduction of the duration of neutropenia and the incidence of febrile neutropenia in patients treated with established cytotoxic chemotherapy for malignancy (with the exception of chronic myelogenous leukemia and myelodysplastic syndromes) and reduction in the duration of neutropenia in patients undergoing myeloblastic therapy followed by bone marrow transplantation considered to be at increased risk of prolonged severe neutropenia. This safety and efficacy of filgrastim are similar in adults and children receiving cytotoxic chemotherapy.
-
Mobilization of peripheral blood progenitor cells.
-
In patients (children or adults) with severe congenital, cyclic, or idiopathic neutropenia with an absolute neutrophil count (ANC) of 0,5 × 109/L, and a history of severe or recurrent infections, long-term administration is indicated to increase neutrophil counts and to reduce the incidence and duration of infection-related events.
-
Treatment of persistent neutropenia (ANC 1,0 × 109/L) in patients with advanced HIV infection in order to reduce the risk of bacterial infections when other therapeutic options are inappropriate.
Biosimilar G-CSFs
Biograstim/filgrastim ratiopharm/ratiograstim/tevagrastim (XM02)
Active substance
Presentation
Clinical studies
Clinical efficacy
Safety
Trade name | Common name (INN) | Biosimilar sponsor | Reference product |
---|---|---|---|
Biograstim® | Filgrastim | CT Arzneimittel GmbH | Neupogen® |
Filgrastim ratiopharm® | Filgrastim | Ratiopharm GmbH | Neupogen® |
Ratiograstim® | Filgrastim | Ratiopharm GmbH | Neupogen® |
Tevagrastim® | Filgrastim | Teva Generics GmbH | Neupogen® |
Zarzio® | Filgrastim | Sandoz | Neupogen® |
Filgrastim HEXAL® | Filgrastim | Hexal | Neupogen® |
Nivestim® | Filgrastim | Hospira | Neupogen® |
Zarzio/filgrastim hexal | Biograstim/filgrastim ratiopharm/ratiograstim/tevagrastim (XM02) | Nivestim | |
---|---|---|---|
Product characteristics | |||
Produced | E. Coli | E. Coli | E. Coli |
Strength | Two strengths: 30 MU/0.5 ml and 48 MU/0.5 ml. | Two strengths: 30 or 48 MIU (corresponding to 300 and 480 μg respectively). | Three strengths: 120 μg/0.2 ml, 300 μg/0.5 ml and 480 μg/0.5 ml. |
Medicinal product | Product composition of Zarzio and Neupogen® are quantitatively identical except the buffer system, glutamate for Zarzio and acetate for Neupogen® | Buffered with acetate. Differs from Neupogen® only in pH and in the concentration of filgrastim and polysorbate 80. | Buffered with acetate. |
Pre-clinical data | |||
Studies | 6 primary PD studies (4 in vitro); 3 toxicology studies (comparative repeat-dose toxicity, toxicokinetics, local tolerance; no single-dose toxicity study); no secondary PD studies; no safety pharmacology studies; no PK studies | 6 primary PD studies (3 in vitro); 1 secondary PD study (in vitro); 3 safety pharmacology studies; 2 PK studies; 6 toxicology studies (repeat dose toxicity study non-comparative) | Primary PD studies: PD response was determined in a neutropenic rat model, as well as in healthy rat in a repeat-dose toxicity study; no secondary PD studies; no safety pharmacology studies; PK assessed as part of the repeat-dose toxicity study; no single-dose toxicity study |
Clinical data | |||
Phase I (PK/PD) studies | 4 PK/PD studies in healthy volunteers | 2 PK/PD studies in healthy volunteers | 2 PK/PD studies in healthy voluteers |
Phase III studies | 1 non-controlled study in patients with breast cancer | 3 RCTS (patients with breast cancer, lung cancer, NHL) | 1 RCT in patients with breast cancer |
Efficacy data | Similar to Neupogen® The comparability of the efficacy based on a PPD study in healthy volunteers (absolute neutrophile and CS34+ cell counts) was considered acceptable by the CHMP. | Similar to Neupogen® There were no statistically significant differences between XM02 and Neupogen® with regard to the mean ANC nadir and with regard to time to ANC recovery in the studies. | Similar to Neupogen® There was therapeutic equivalence between the two products in terms of efficacy with regard to the mean ANC nadir and with regard to time to ANC recovery. |
Safety data | Similar to Neupogen® | Similar to Neupogen® | Similar to Neupogen® |