According to the RMP, this refers to risks (other updated ‘fistulae a study completed in 2010. In the than GI)’ and version of the ‘cardiac response the sponsor should disorders (exc. CHF and ASA with provide information on whether ATE)’. their this activity is completed and ACPM should therefore be removed from response. the pharmacovigilance plan. The evaluator maintains the The following statement This is following recommendations has been proposed for acceptable. regarding the draft product inclusion in the information made in a previous Precautions section of evaluation for bevacizumab: the Avastin PI via That the specific term Safety-Related Request ‘physeal dysplasia’should be added to the which is currently nonclinical section of the PI to be under review by TGA: consistent with the EU Summary of a 26 week ‘In Product Characteristics (SmPC) and trial in communicate this important cynomolgus monkeys, potential risk. physeal dysplasia was That under ‘Precautions-wound observed in young healing’ a statement such as the animals with open following found in the SmPC should growth plates, at be added: wound healing ‘Serious bevacizumab average complications, including serum concentrations anastomotic complications, have below the expected been reported, some of which had a human therapeutic fatal outcome ‘. average serum concentrations.’ The following statement has been proposed for inclusion in the Precautions section of the Avastin PI via Safety-Related Request PM-2014-01869-1-4 which is currently under review by TGA: wound healing ‘Serious complications, including anastomotic complications, have been reported, some of which had a fatal outcome. ‘ Summary of recommendations It is considered that the sponsor’s response to the TGA’s request for further information has adequately addressed all of the issues identified in the RMP evaluation report.
According to the RMP, this refers to a study completed in 2010. In the response the sponsor should provide information on whether this activity is completed and should therefore be removed from the pharmacovigilance plan. risks ‘fistulae (other than GI)’ and ‘cardiac disorders (exc. CHF and ATE)’. updated version of the ASA with their response. The evaluator maintains the following recommendations regarding the draft product information made in a previous evaluation for bevacizumab: That the specific term ‘physeal dysplasia’should be added to the nonclinical section of the PI to be consistent with the EU Summary of Product Characteristics (SmPC) and communicate this important potential risk. That under ‘Precautions-wound healing’ a statement such as the following found in the SmPC should be added: ‘Serious wound healing complications, including anastomotic complications, have been reported, some of which had a fatal outcome ‘. The following statement has been proposed for inclusion in the Precautions section of the Avastin PI via Safety-Related Request which is currently under review by TGA: ‘In a 26 week in cynomolgus monkeys, physeal dysplasia was observed in young animals with open growth plates, at bevacizumab average serum concentrations below the expected human therapeutic average serum concentrations.’ The following statement has been proposed for inclusion in the Precautions section of the Avastin PI via Safety-Related Request PM-2014-01869-1-4 which is currently under review by TGA: ‘Serious wound healing complications, including anastomotic complications, have been reported, some of which had a fatal outcome. ‘ This is acceptable. Summary of recommendations It is considered that the sponsor’s response to the TGA’s request for further information has adequately addressed all of the issues identified in the RMP evaluation report. ACPM trial
auspar-bevacizumab-150311.docx