Module S.VII.5: The sponsor has It would appear that the ‘Pharmacological Effects’ of the EU-RMP provided justification clinical data indicate that states inter alia: to other as to why none of the the incidence of “Similar ‘Vitamin approved PBs, GI events (such as specified deficiency’ in the nausea, vomiting, diarrhoea, and pharmacological class Velphoro treatment arm constipation) are the most effects should be (2.26%) is comparable if common adverse events reported” considered as ongoing not slightly higher than and are no safety concerns (see the incidence from the “There pharmacological class effects Issues’ sevelamer carbonate ‘Outstanding considered as important identified below). group (1.72%). or potential risks.” Nevertheless Consequently it is the sponsor indicates that in the recommended that the pivotal studies Velphoro had no pharmacological class marked differences in safety effect: Deficiency’ ‘Vitamin profile compared to sevelamer. be adopted for Velphoro Consequently the sponsor should as an important potential provide compelling justification risk which may be as to why the following ongoing monitored by routine safety concerns associated with pharmacovigilance. Given sevelamer should not be adopted the background routine for Velphoro: risk minimisation will not be required for this the important identified risks: ongoing safety concern. Deficiency’, ‘Vitamin ‘Peritonitis’ These changes need only & of metabolic ‘Worsening be reflected in a revised acidosis’ ASA before this the important potential risks: application is approved. Obstruction/ileus’, ‘Intestinal CKD ‘Hyperphosphataemic patients on peritoneal dialysis’, fistula site adverse reactions’ ‘AV and sodium chloride ‘Increased levels’. If the sponsor decides to include these ongoing safety concerns in Australia for Velphoro, then consideration must be given as to what pharmacovigilance and risk minimisation activities will be proposed for them and the ASA should be revised accordingly. Notwithstanding the evaluation The sponsor has See cell below. of the nonclinical and clinical provided justification aspects of the Safety as to why none of the Specifications, it is recommended proposed important that the sponsor consider the potential should following amendments (shown in be considered as the following row) to this list of ongoing safety ongoing safety concerns: concerns.
Module S.VII.5: ‘Pharmacological Effects’ of the EU-RMP states inter alia: “Similar to other approved PBs, GI events (such as nausea, vomiting, diarrhoea, and constipation) are the most common adverse events reported” and “There are no pharmacological class effects considered as important identified or potential risks.” Nevertheless the sponsor indicates that in the pivotal studies Velphoro had no marked differences in safety profile compared to sevelamer. Consequently the sponsor should provide compelling justification as to why the following ongoing safety concerns associated with sevelamer should not be adopted for Velphoro: the important identified risks: ‘Vitamin Deficiency’, ‘Peritonitis’ & ‘Worsening of metabolic acidosis’ the important potential risks: ‘Intestinal Obstruction/ileus’, ‘Hyperphosphataemic CKD patients on peritoneal dialysis’, ‘AV fistula site adverse reactions’ and ‘Increased sodium chloride levels’. If the sponsor decides to include these ongoing safety concerns in Australia for Velphoro, then consideration must be given as to what pharmacovigilance and risk minimisation activities will be proposed for them and the ASA should be revised accordingly. The sponsor has provided justification as to why none of the specified pharmacological class effects should be considered as ongoing safety concerns (see ‘Outstanding Issues’ below). It would appear that the clinical data indicate that the incidence of ‘Vitamin deficiency’ in the Velphoro treatment arm (2.26%) is comparable if not slightly higher than the incidence from the sevelamer carbonate group (1.72%). Consequently it is recommended that the pharmacological class effect: ‘Vitamin Deficiency’ be adopted for Velphoro as an important potential risk which may be monitored by routine pharmacovigilance. Given the background routine risk minimisation will not be required for this ongoing safety concern. These changes need only be reflected in a revised ASA before this application is approved. Notwithstanding the evaluation of the nonclinical and clinical aspects of the Safety Specifications, it is recommended that the sponsor consider the following amendments (shown in the following row) to this list of ongoing safety concerns: The sponsor has provided justification as to why none of the proposed important potential should be considered as ongoing safety concerns. See cell below.
auspar-sucroferric-oxyhydroxide-150219.docx