Regulatory Decision Summary for EMEND IV

Fosaprepitant (a prodrug of aprepitant) is currently indicated for the prevention of chemotherapy induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC) in both women and men, and due to moderately emetogenic chemotherapy (MEC) in women only. The purpose of this Supplement to a New Drug Submission (SNDS) was to modify the indication of Emend IV (fosaprepitant) to include males for the prevention of nausea and vomiting due to MEC. To support this requested change, the sponsor provided new data from a clinical trial that enrolled both men (41%) and women (59%) with various forms of cancer who were being treated with MEC. The results of the study showed a statistically significant effect on the primary endpoint, as well as on one key secondary endpoint; while statistical results for the second key secondary endpoint were non-significant. Specifically, the addition of fosaprepitant to the standard therapy regimen in the MEC setting showed statistically significant results in the delayed phase (25 to 120 hours) and overall (0 to 120 hours) phase following the initiation of MEC, but not in the acute phase (0 to 24 hours) when analysed separately.

Although the primary and secondary endpoints favored the addition of fosaprepitant to standard therapy in the treatment of CINV due to MEC, these effects were in large part driven by women, as was the case in a previous study conducted with aprepitant in the MEC setting. It is noted however that these studies were not powered to evaluate efficacy in gender-based subpopulations and that the trends in efficacy still favored treatment with fosaprepitant in females. Given that no study has analyzed males specifically, as was done in females with aprepitant, the additional benefit to standard therapy in the MEC setting for men is not well defined. Nevertheless, the efficacy data in males in both studies was overall favourable and fosaprepitant has been indicated in males in both the European Union (EU) and United States (US) for some years now, which supports efficacy in men.

No safety issues have arisen in males distinct from females in the EU and US, and no safety issues were identified in males that differed from those in females in the sponsors clinical trial database. Finally, the cancer care treatment guidelines do not distinguish between males and females in their recommended care for CINV, unless to provide specific recommendations for cyclophosphamide- and anthrocycline-based treatments in women with breast cancer. Taken together, there appears to be no reason to limit the indication to women only in the MEC setting and, therefore, an indication in men, as requested by the sponsor, was granted.