Risk minimisation activities The sponsor concludes that routine risk minimisation activities for all the specified safety concerns and missing information are sufficient, except for the important potential risk: and the missing information: with severe cardiac impairment’, ‘Neuropathy’ ‘Patients safety’ and use of ceritinib and gastric acid agents such ‘Long-term ‘Concomitant as PPIs’ for which no risk minimisation activities are proposed. Reconciliation of issues outlined in the RMP report Table 8 summarises the first round evaluation of the RMP, the sponsor’s responses to issues raised by the evaluator and the evaluation of the sponsor’s responses. 8: Reconciliation of issues outlined in the RMP Evaluation Report Recommendation in RMP Sponsor’s response RMP evaluator’s evaluation report comment Safety considerations may The nonclinical The sponsor be raised by the nonclinical report have now states: this time ‘At and clinical evaluators become available no specific issues through the consolidated and the sponsor have been raised section request and/or the should now by the Clinical Nonclinical and Clinical adequately address Evaluator Evaluation Reports any outstanding regarding the EU respectively. It is important issues (see Section RMP submitted to ensure that the 2: on the ‘Comments and the Nonclinical information provided in safety specification Evaluation Report response to trial includes a of the RMP’), first round is not consideration of the preferably before available at this relevance for the Risk this application is time’. Management Plan and any approved. specific information needed to address this issue in the RMP. For any safety considerations so raised, the sponsor should provide information that is relevant and necessary to address the issue in the RMP. Consistent with the US FDA This is acceptable. The sponsor has ‘Postmarketing provided Requirements’, the justification and important potential risk: concluded: from drug ‘Toxicity ‘modeling when taken with demonstrates that food’ should be included as even if a patient a new safety concern. took ceritinib at Consideration must be given 750 mg daily with as to what food, the expected pharmacovigilance and risk increased exposure minimisation activities will would not result in be proposed for this new a QT prolongation safety concern and only the beyond 21.6 ms, ASA need be revised indicating a low accordingly. risk of increased toxicity driven by
Risk minimisation activities The sponsor concludes that routine risk minimisation activities for all the specified safety concerns and missing information are sufficient, except for the important potential risk: ‘Neuropathy’ and the missing information: ‘Patients with severe cardiac impairment’, ‘Long-term safety’ and ‘Concomitant use of ceritinib and gastric acid agents such as PPIs’ for which no risk minimisation activities are proposed. Reconciliation of issues outlined in the RMP report Table 8 summarises the first round evaluation of the RMP, the sponsor’s responses to issues raised by the evaluator and the evaluation of the sponsor’s responses. 8: Reconciliation of issues outlined in the RMP Evaluation Report Recommendation in RMP evaluation report Sponsor’s response RMP evaluator’s comment Safety considerations may be raised by the nonclinical and clinical evaluators through the consolidated section request and/or the Nonclinical and Clinical Evaluation Reports respectively. It is important to ensure that the information provided in response to includes a consideration of the relevance for the Risk Management Plan and any specific information needed to address this issue in the RMP. For any safety considerations so raised, the sponsor should provide information that is relevant and necessary to address the issue in the RMP. The sponsor states: ‘At this time no specific issues have been raised by the Clinical Evaluator regarding the EU RMP submitted and the Nonclinical Evaluation Report first round is not available at this time’. The nonclinical report have now become available and the sponsor should now adequately address any outstanding issues (see Section 2: ‘Comments on the safety specification of the RMP’), preferably before this application is approved. Consistent with the US FDA ‘Postmarketing Requirements’, the important potential risk: ‘Toxicity from drug when taken with food’ should be included as a new safety concern. Consideration must be given as to what pharmacovigilance and risk minimisation activities will be proposed for this new safety concern and only the ASA need be revised accordingly. The sponsor has provided justification and concluded: ‘modeling demonstrates that even if a patient took ceritinib at 750 mg daily with food, the expected increased exposure would not result in a QT prolongation beyond 21.6 ms, indicating a low risk of increased toxicity driven by This is acceptable. trial
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