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Replies to post #126188 on Biotech Values
09/06/11 10:16 AM
Based on our review of the clinical data, we recommend a complete response [i.e. non-approval]. Reasons for this recommendation include:
1. There is a lack of substantial evidence that rivaroxaban will have its desired effect when used as recommended in labeling. (21 CFR 314.125(b)(5)). The data from the Sponsor’s Phase 3 ROCKET trial comparing rivaroxaban to warfarin are not adequate to determine whether rivaroxaban is as effective for its proposed indication in comparison to warfarin when the latter is used skillfully (e.g., TTR >~68%, near the midpoint of center based TTR in the RE-LY study, and the US median TTR of 65% in ROCKET). In order for atrial fibrillation (AFib) patients to be protected from the risk of thrombotic events, a new drug for this indication should be demonstrated to be as effective as warfarin when it is used skillfully [“skillfully” is the key word]…
2. There is insufficient information about the drug to determine whether it is safe for use with its proposed labeling (21 CFR 314.125(b)(4)). In the ROCKET study there was an excess of strokes in the rivaroxaban arm during the transition from blinded study drug to open label warfarin at the end of the study. The Sponsor’s proposed instructions for the transition from rivaroxaban to warfarin, developed after ROCKET was completed, have not been evaluated or shown to be safe in terms of bleeding risk or embolic risk in a clinical study. Such a study must be performed prior to approval in this case (see Section 6.1.10.3.7 for a discussion of this issue). The study of the transition regimen could be performed as part of the study needed to satisfy the deficiency cited in paragraph 1, above [ouch].
09/08/11 5:52 PM
09/23/11 8:38 AM
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