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FDA reviewers question Vibativ efficacy, safety

November 28, 2012 1:56 AM UTC

FDA reviewers outlined safety concerns and trial design issues identified in a resubmitted NDA for Vibativ telavancin from Theravance Inc. (NASDAQ:THRX) to treat nosocomial pneumonia (NP), including ventilator-associated pneumonia known or suspected to be caused by methicillin-resistant Staphylococcus aureus (MRSA). In briefing documents released ahead of FDA's Anti-Infective Drugs Advisory Committee Thursday meeting to discuss the NDA, the reviewers questioned "inconsistencies" in clinical response data for Vibativ from the Phase III Study 0015 and 0019 trials, noting that there were a "large number of patients" who were considered clinical cures, the primary endpoint, at the test of cure evaluation but who subsequently died by day 28. The reviewers also noted that in a post-hoc analysis using 28-day all-cause mortality as the endpoint, the morality rate with Vibativ in Study 0015 was "almost significantly higher" than with vancomycin (p=0.06). The difference was not significant in Study 0019.

Additionally, the reviewers said a "high proportion" of patients in both trials received concomitant antibacterials for Gram-negative coverage that also cover Gram-positive bacteria, which "may substantially confound" Vibativ's efficacy for NP, a Gram-positive infection. The reviewers also said that in patients with baseline risk factors for renal impairment, Vibativ is associated with higher mortality and lower cure rates than vancomycin. The reviewers did note that the potential nephrotoxicity risk with Vibativ is consistent with warnings in the drug's current label. ...