Regulatory Decision Summary for JADENU

The sponsor is seeking approval of its new formulation of deferasirox, under the name of Jadenu, based on the PK comparability to the currently approved DT formulation. The currently approved product, Exjade, has been shown to be an effective oral iron chelator; however, poor palatability, a difficult administration and a food effect may have been adversely affecting patient tolerance and compliance.

The sponsor has developed a dose-adjusted film-coated formulation of deferasirox named Jadenu. In the pivotal PK comparability study conducted in healthy volunteers, this new formulation at a 28% reduced strength was shown to be comparable to the dispersible tablet formulation in terms of exposure, but demonstrated a 30% increase in peak concentration, exceeding Health Canada’s standard for comparative bioavailability. The sponsor provided credible evidence to confirm the lack of a clinically meaningful effect of the increase in peak concentration on the efficacy or safety of the new formulation.

In this study, no significant difference in the safety profiles of the dispersible tablet and film-coated tablet formulations was apparent. Exjade contains lactose and sodium lauryl sulfate, which may cause gastrointestinal side effects. The sponsor had suggested that the exclusion of lactose and sodium lauryl sulfate from the Jadenu formulation may improve tolerability. The incidence of gastrointestinal adverse events in the study does not support this conclusion: there were 8 events reported following dosing with Jadenu, and 3 events following dosing with Exjade.

No new data were submitted with regard to efficacy; and limited new safety data were submitted. As the two formulations have comparable exposures, the new film-coated formulation is expected to have comparable efficacy and safety. A pharmacokinetic/pharmacodynamic analysis provided additional confirmation on the influence of exposure on efficacy and safety; and the unlikelihood that the difference in peak concentration would affect safety.

Overall, Jadenu, a new formulation of deferasirox, has a positive risk-benefit evaluation. The dose-adjusted new formulation is considered therapeutically comparable to the currently available dispersible formulation Exjade, with the benefits of a reduced food effect, improved palatability, and more convenient mode of administration.