SILVER SPRING, MD. – The approval of the antibacterial drug telavancin should be expanded to include patients with nosocomial pneumonia, but only in limited situations, according to the majority of a Food and Drug Administration advisory panel.
At a meeting Nov. 29, the FDA’s Anti-Infective Drugs Advisory Committee voted 13-2 that the available data on telavancin provided substantial evidence that it was safe and effective for treating nosocomial pneumonia, "when other alternatives are not suitable." Panelists agreed that telavancin should be reserved to treat patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) not methicillin-sensitive S. aureus (MSSA) or Streptococcus pneumoniae, because there are many other treatments available for those infections.
Most panelists did not support approval of the broader indication requested by the manufacturer: treatment of patients with nosocomial pneumonia, including ventilator-associated pneumonia (VAP), caused by susceptible isolates of the Gram-positive microorganisms, S. aureus (including methicillin-susceptible and methicillin-resistant isolates) or S. pneumoniae. The panel voted 9-6 that the data from the two studies did not provide substantial evidence that the drug was safe and effective for this indication.
Telavancin is a lipoglycopeptide antibacterial administered intravenously, with bactericidal activity that results from inhibition of cell wall synthesis and disruption of bacterial plasma membrane function, according to Theravance, the drug’s manufacturer. It was approved in 2009 for the treatment of adults with complicated skin and skin structure infections caused by susceptible Gram-positive bacteria and is marketed as Vibativ.
The current labeling for telavancin includes warnings and precautions in the prescribing information about the increased risk of nephrotoxicity associated with treatment, based on experience in patients treated for the skin infection indication. A boxed warning cites the potential fetal risks.
Among the other points made by panelists were that labeling should include statements about use in patients with reduced creatinine clearance and renal failure and that the company should aggressively collect postmarketing safety and efficacy data.
The panel considered data that included analyses of clinical cure and 28-day all-cause mortality from two non-inferiority studies. These studies comprised 1,503 patients with nosocomial pneumonia and compared telavancin for 7-21 days (10 mg/kg every 24 hours administered intravenously in patients with normal renal function and mild renal impairment or an adjusted dose for patients with moderate or severe renal insufficiency) with vancomycin (1 g IV every 12 hours).
Theravance first submitted an application for approval of the broad nosocomial pneumonia indication in 2009. That application included results of the two studies, which used clinical cure rate as the primary endpoint. Since then, the FDA has requested more data from the company, including a post hoc analysis of mortality, but subsequently declined to approve telavancin after deciding that the trials did not provide adequate evidence of non-inferiority to vancomycin. In response, the company filed a formal dispute, which was rejected by the FDA, but the agency encouraged the company to resubmit the application and held the panel meeting Nov. 29 to review the data.
Telavancin has been approved in the European Union for the treatment of nosocomial pneumonia caused by MRSA, similar to the indication backed by the FDA panel.
The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although a panelist may occasionally be given a waiver, but not at this meeting.