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.
potential for medication errors. ‘Risk Minimisation Activities Referenced in the EU-RMP’ of the ASA states: “In addition to routine pharmacovigilance measures, the following additional pharmacovigilance activity will occur. 1. Evaluation of the PIP [paediatric investigation plan] will monitor the safety profile of Velphoro in children and adolescents.” The sponsor should amend this section of the ASA as it is inappropriate to refer to pharmacovigilance activities in the Risk Minimisation Plan. The sponsor states: “The applicant will provide an amended statement in the next version of the revised ASA for Section 3.1 ‘Risk Minimisation Activities Referenced in the EU-RMP’.” The sponsor should now make such changes and submit a revised ASA before this application is approved. The sponsor should provide a table summarising the pharmacovigilance plan and risk minimisation plan proposed for Australia in the ASA. Wording pertaining to all the specified ongoing safety concerns in the proposed Australian PI and CMI should be included in the table. The sponsor states: “To summarise the pharmacovigilance plan and risk minimisation plan planned for Australia for the ongoing safety concerns, the applicant will include [a] Table into the next version of the revised ASA. The proposed text in the table below is presenting the current wording of the proposed Australian Reference Safety Information.” The sponsor should now make such changes, taking into account ‘Outstanding issues’ (see above), and submit a revised ASA before this application is approved. Notwithstanding the recommendations made in regard to the specified list of ongoing safety concerns, the proposed routine risk minimisation activities in the product information document are considered satisfactory. Similarly in regard to the proposed routine risk minimisation activities, the draft CMI is considered satisfactory. The sponsor agrees that the proposed routine risk minimisation activities are sufficient for the specified list of ongoing safety concerns. n/a