increased systemic exposure caused by food intake. Therefore, the applicant does not consider that that from drug ‘Toxicity over‐exposure when taken with food’ should be included as a new safety concern’. As previously stated The sponsor The sponsor has consideration must be given states: documented this ‘As as to what indicated in undertaking in the pharmacovigilance activities response to updated ASA and will be proposed for the new Recommendation this is acceptable. important potential risk: 2, the Applicant from drug ‘Toxicity does not consider when taken with that from ‘Toxicity food’. To that end the drug over‐exposure sponsor should at least when taken with include the US FDA food’ should be required clinical trial to included as a new evaluate the systemic safety concern, exposure and safety of 450 therefore no mg Zykadia (ceritinib) taken pharmacovigilance with a meal and 600 mg activities are Zykadia (ceritinib) taken proposed. Although with a light meal as Novartis does not compared with that of 750 propose to add mg Zykadia (ceritinib) taken from drug ‘Toxicity in the fasted state in over‐exposure metastatic ALK-positive when taken with NSCLC patients as an food’ to the additional summary of pharmacovigilance activity ongoing safety for this new safety concern. Only the ASA need be concerns at this revised accordingly and it is time, effects on expected that at least a draft drug exposure due protocol for this study will to food be attached to the revised interactions will be ASA. evaluated in Study A2112 as previously discussed. When the US FDA The sponsor has This approved the ALK-positive objected to this recommendation NSCLC indication this recommendation remains outstanding approval stated: ‘This and provided for the Delegate’s indication is approved justification for consideration. under accelerated approval their position. based on tumor response rate and duration of
increased systemic exposure caused by food intake. Therefore, the applicant does not consider that that ‘Toxicity from drug over‐exposure when taken with food’ should be included as a new safety concern’. As previously stated consideration must be given as to what pharmacovigilance activities will be proposed for the new important potential risk: ‘Toxicity from drug when taken with food’. To that end the sponsor should at least include the US FDA required clinical trial to evaluate the systemic exposure and safety of 450 mg Zykadia (ceritinib) taken with a meal and 600 mg Zykadia (ceritinib) taken with a light meal as compared with that of 750 mg Zykadia (ceritinib) taken in the fasted state in metastatic ALK-positive NSCLC patients as an additional pharmacovigilance activity for this new safety concern. Only the ASA need be revised accordingly and it is expected that at least a draft protocol for this study will be attached to the revised ASA. The sponsor states: ‘As indicated in response to Recommendation 2, the Applicant does not consider that ‘Toxicity from drug over‐exposure when taken with food’ should be included as a new safety concern, therefore no pharmacovigilance activities are proposed. Although Novartis does not propose to add ‘Toxicity from drug over‐exposure when taken with food’ to the summary of ongoing safety concerns at this time, effects on drug exposure due to food interactions will be evaluated in Study A2112 as previously discussed. The sponsor has documented this undertaking in the updated ASA and this is acceptable. When the US FDA approved the ALK-positive NSCLC indication this approval stated: ‘This indication is approved under accelerated approval based on tumor response rate and duration of The sponsor has objected to this recommendation and provided justification for their position. This recommendation remains outstanding for the Delegate’s consideration.
auspar-zykadia-270218.docx