Regulatory Decision Summary for Gadovist

While two studies (91743 and 91782) were submitted in support of contrast-enhanced MRI of the breast, only Study 91782 was considered confirmatory for the sought indication. The amended objective of the study was met; the superiority of within-patient sensitivity of combined unenhanced and Gadovist-enhanced breast MRI (CMRM) over unenhanced breast MRI (UMRM) was demonstrated. Breast level specificity of CMRM met the pre-defined success criterion. The study results support the extension of the indication to Gadovist-enhanced MRI of the breast to assess the presence and extent of malignant breast disease.

Study 304561 was submitted in support of contrast-enhanced MRI of the kidney. The objective of the study was met; the statistical difference between Gadovist and Magnevist was observed for the accuracy rate and Gadovist was proven non-inferior to Magnevist in terms of diagnostic accuracy. The evidence supports the extension of the Gadovist indications to enhanced MRI of the kidney.

Study 304562 was submitted in support of liver MRI. The results of the per-protocol primary efficacy variable analysis failed to demonstrate non-inferiority of Gadovist to the comparator. The primary efficacy variable was changed from diagnostic accuracy to increase in diagnostic accuracy from pre-contrast to combined pre- post-contrast MRI; the non-inferiority margin was also changed. The results of the amended analysis also failed to demonstrate the non-inferiority of Gadovist over Magnevist; therefore, the indication for Gadovist-enhanced liver MRI could not be granted.

Study 305501 and a literature review were submitted in support of cardiac MRI. The study was a Phase II dose-finding study. The results of the study failed to meet the study objective; the most efficacious dose could not be determined with certainty. Furthermore, the results of literature review also failed to provide additional evidence in support of the cardiac MRI element of the indication; therefore, Gadovist-enhanced cardiac MRI could not be granted.

Study 13297 was submitted and a literature review in support of the whole body imaging indication. The overall objective of the study was met; the study demonstrated that Gadovist is non-inferior to Magnevist in terms of the quality of imaging. The results demonstrated that technical performance of Gadovist is not inferior to that of Magnevist. Diagnostic performance of Gadovist in terms of sensitivity/specificity for the detection of malignant lesions was dependent on the body regions. The clinical significance of such results could not be determined. Overall, the study did not provide sufficient evidence to support the Gadovist-enhanced MRI of the whole body. The literature review failed to provide evidence to demonstrate the extent to which the submitted data mirrors the proposed indication for use in terms of dosing, population, intervention, and outcome measures.

In terms of safety, no unexpected adverse events (AEs) were reported from the clinical studies submitted in support of this SNDS. All reported AEs are already included in the current Product Monograph (PM).

In conclusion, the benefit-risk profile of the drug remains favourable. A few uncertainties about the risk of the drug administration in the proposed population remain which are properly labelled in the PM. The evidence of clinical efficacy is not robust enough to extend the indication to contrast-enhanced MRI of whole body. However, the data in this submission was sufficient to extend the use of Gadovist to contrast-enhanced MRI of the breast and kidney.