On November 29th, 2012, the FDA’s Anti-Infective Drugs Advisory Committee voted 13-2 to recommend telavancin (Vibativ®) for the treatment of nosocomial pneumonia including hospital- and ventilator-acquired pneumonia (HAP, VAP) caused by MRSA in seriously ill patients for whom no other suitable alternatives exist. The FDA advisory panel voted 9-6 against recommending telavancin as first-line treatment of MRSA nosocomial pneumonia. The drug is not recommended for Streptococcus pneumoniae infections.
The primary reasons for the panel’s limited recommendation were concerns over a trend towards increased mortality in patients taking telavancin vs. vancomycin in one of the two studies submitted with the drug’s NDA, and a trend towards higher renal function impairment in the telavancin group.
In two double-blind studies (ATTAIN trials, study 0015 and 0019), a total of 1503 patients with HAP caused by gram-positive bacteria, including MRSA, were randomized 1:1 to receive telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h). In the pooled all-treated population, cure rates with telavancin vs. vancomycin were 58.9% vs. 59.5% (95%CI for difference: 5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference: 4.3% to 7.7%). Mortality rates for telavancin-treated vs. vancomycin-treated patients were 21.5% vs. 16.6% (95% CI for the difference: 0.7% to 10.6%) for study 0015, and 18.5% vs. 20.6% (95% CI for the difference: 7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs. 10%). Additional details on the design and results of the ATTAIN trials may be found here.
Although telavancin showed similar efficacy to vancomycin (non-inferiority) in the ATTAIN studies, the mortality trend seen in study 0015 concerned members of the FDA advisory panel. However, the company said that the increased mortality was seen primarily in patients with creatinine clearance values
Telavancin in sepsis treatment
Telavancin was previously studied in a small trial (ASSURE, n=58, 31 completed) for the treatment of gram-positive bacteremia vs. standard treatment with vancomycin. The study showed similar efficacy to vancomycin, but was too small to be statistically significant. Additional information on ASSURE can be found here.
Another phase 2 trial (estimated enrollment n=40) examining telavancin’s efficacy in sepsis is currently under way and recruiting at the University of Texas MD Anderson Cancer Center. More information on this trial may be found here.
General drug information
Telavancin (Vibativ) is a semi-synthetic bacterial lipoglycopeptide derivative of vancomycin developed by and marketed in the US by Theravance for the treatment gram-positive skin infections, including infections with MRSA. The drug was approved by the FDA in 2009 for the treatment of complicated skin and skin structure infections (cSSSI). Telavancin received EU marketing authorization by EMEA in September of 2011 for the treatment nosocomial pneumonia including HAP and VAP suspected to be caused by MRSA. However, in May 2012, the European Commission suspended this marketing authorization because the single-source drug product supplier (Ben Venue Laboratory, Ohio) did not meet the Good Manufacturing Practice (GMP) requirements. The drug remains suspended in the EU and has never been on the market there.
Daniel Nichita, MD
This article is strictly informational. ESCAVO does not endorse the use of any drugs mentioned in this article and has no relationship with any of the companies or organizations listed within. The drugs and indications discussed may not be FDA approved. Use caution and your own clinical judgment when deciding to use any drugs or treatments discussed in this news feed.