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Ratiograstim / Tevagrastim (G-CSF)

Original article by: Alexandra Denby

Source: London New Drugs Group

Keywords: G-CSF, filgrastim, ratiograstim, tevagrastim, XM02

Date published: 23/02/2010 11:00

Summary
by: Alexandra Denby
  • Ratiograstim and Tevagrastim are biosimilar G-CSF products. Both contain the bacterially synthesised, non-glycosylated recombinant methionyl form of human G-CSF (known as XM02).
  • Both products are approved for the same indications as Neupogen, which include cytotoxic-induced neutropenia, mobilisation of peripheral blood progenitor cells, severe chronic neutropenia (congenital, cyclic or idiopathic) and persistent neutropenia in HIV infection.
  • In the two phase II pharmacokinetic/pharmacodynamic studies mean serum concentration profiles over time (area under the curve over 48 hours, AUC) of XM02 were similar to those of Neupogen.  Both AUC and maximum concentrations were in the 80-125% acceptance intervals for all dose regimens.  Absolute neutrophil count profiles were similar for both XM02 and Neupogen.
  • There are three main phase III studies.  The pivotal study was a placebo-controlled study in patients with breast cancer; the two supportive studies were carried out in patients with lung cancer and with Non-Hodgkin Lymphoma (NHL).  In the three studies the effects of XM02 on the duration and severity of neutropenia were similar to those seen with Neupogen.
  • The most common G-CSF-related treatment-emergent adverse events were bone pain, diarrhoea, asthenia, myalgia, arthralgia, headache and pyrexia, all of which are known adverse events of G-CSF.  A similar side effect profile was seen for all cycles (XM02 vs. Neupogen).
  • There are inconsistencies between the studies in the incidences of febrile neutropenia, which may be due to the myelotoxicity of the different chemotherapy regimens used and different cancers treated.  A meta-analysis calculated the estimated common risk (weighted arithmetic mean of the individual risks) to be 1.7, with an odds ratio of FN (XM02 vs. filgrastim) of 1.08.  Both of these statistical tests imply that FN was more likely to occur with XM02 treatment.
  • The efficacy of XM02 has only been shown in trials with cytotoxic chemotherapy and not the other indications for which they are also approved. This follows the EMEA guidelines, that if clinical comparability in chemotherapy-induced neutropenia is demonstrated, the results can be extrapolated to the other indications of the biological product.
  • Filgrastim should be prescribed by brand name to enable pharmacovigilance and to ensure that adverse drug reactions are properly assigned to the correct product.  If reporting an adverse drug reaction, the brand name must be used.
Ratio_Tevagrastim_Feb2010.pdf

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