2.1.5.13.3 of Module 2.7.4 provided with the GIST submission). Severe liver injury reported from data (6/30,000) and the ongoing Study 15967 (CONSIGN) (1/3000) indicate that the frequency of severe liver injury is not higher but rather lower compared to the time of first (CRC) submission (3 cases in around 1200 regorafenib-treated cancer patients; see M2.7.4 provided with the CRC submission). Therefore, the information presented in the Precautions Hepatotoxicity and Dosage – and Administration - Table 9 - Recommended measures and dose modifications in case of drug related liver function test abnormalities section of the PI provides adequate liver monitoring and dosing guidance for both indications, CRC and GIST. Experience with the label-defined LFT monitoring schedule indicates that this approach is acceptable.’ In the section, considers the current This is considered ‘Precautions’ ‘Bayer under a separate heading, approach in the PI describing acceptable in the the PI should include a infection as a very common context of this statement on the association ADR together with detailed application subject to of tyrosine kinase inhibitors information on the frequency, approval by the with infections (or a severity and most frequently Delegate. statement to that effect). observed sites of infection within section of ‘Description selected adverse reactions’ provides adequate guidance to physicians. No additional respective wording in the Precautions section is required also taking into – account that there is no associated specific monitoring or dose modification recommendation.’ In the section, wide variety of drugs have This is considered ‘Precautions’ ‘A a separate heading, the been implicated among acceptable in the PI should include a causes of interstitial lung context of this statement on the association disease (ILD), including application subject to of tyrosine kinase inhibitors VEGFR-targeting TKIs. At
2.1.5.13.3 of Module 2.7.4 provided with the GIST submission). Severe liver injury reported from data (6/30,000) and the ongoing Study 15967 (CONSIGN) (1/3000) indicate that the frequency of severe liver injury is not higher but rather lower compared to the time of first (CRC) submission (3 cases in around 1200 regorafenib-treated cancer patients; see M2.7.4 provided with the CRC submission). Therefore, the information presented in the Precautions – Hepatotoxicity and Dosage and Administration - Table 9 - Recommended measures and dose modifications in case of drug related liver function test abnormalities section of the PI provides adequate liver monitoring and dosing guidance for both indications, CRC and GIST. Experience with the label-defined LFT monitoring schedule indicates that this approach is acceptable.’ In the ‘Precautions’ section, under a separate heading, the PI should include a statement on the association of tyrosine kinase inhibitors with infections (or a statement to that effect). ‘Bayer considers the current approach in the PI describing infection as a very common ADR together with detailed information on the frequency, severity and most frequently observed sites of infection within section ‘Description of selected adverse reactions’ provides adequate guidance to physicians. No additional respective wording in the Precautions section is required – also taking into account that there is no associated specific monitoring or dose modification recommendation.’ This is considered acceptable in the context of this application subject to approval by the Delegate. In the ‘Precautions’ section, a separate heading, the PI should include a statement on the association of tyrosine kinase inhibitors ‘A wide variety of drugs have been implicated among causes of interstitial lung disease (ILD), including VEGFR-targeting TKIs. At This is considered acceptable in the context of this application subject to
auspar-regorafenib-151119.docx