The emergence of multidrug-resistant Gram-positive pathogens has created a need for newer antibacterial agents with improved efficacy. Researchers have focused on modifying the antibiotic vancomycin and other glycopeptides by adding hydrophobic substituents in order to improve activity, absorption, distribution, metabolism and excretion. Telavancin is one such novel antibiotic that was found to have multiple mechanisms of action, including inhibition of bacterial cell wall formation and disruption of cell membrane integrity. The agent showed potent activity in vitro and in vivo against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, among other bacterial species. Telavancin was also shown to have good pharmacokinetics and was effective in clinical trials in patients with Gram-positive skin and soft tissue infections and hospital-acquired pneumonia.

Telavancin was associated with a rate of clinical response (87.9 vs. 86.5%) statistically equivalent to that of vancomycin in patients with complicated skin and skin structure infections (cSSSI) in the ATLAS I study. The randomized, double-blind, phase III trial included 855 patients at multiple centers. Treatment consisted of vancomycin 1 g i.v. every 12 hours or telavancin 10 mg/kg i.v. every day for 7-14 days. A clinical response was seen in 85.5 and 87%, respectively, of microbiologically evaluable patients with MRSA infection and in 84.6 and 89.9%, respectively, of those with methicillin-susceptible S. aureus infection. Safety was similar between treatments and noninferiority in efficacy was demonstrated.

Efficacy was also demonstrated in the double-blind, randomized, ATTAIN 1 and ATTAIN 2 phase III clinical studies of telavancin for the treatment of hospital-acquired pneumonia (HAP), including patients with ventilator-associated pneumonia (VAP) caused by Gram-positive bacteria such as MRSA. In each study, telavancin achieved its objective of noninferiority in the all-treated and clinically evaluable patient populations. In the clinically evaluable population from ATTAIN 1 and ATTAIN 2 combined, the clinical cure rate for telavancin was 82.7% compared with 80.9% for vancomycin. In the microbiologically evaluable patients who were infected with MRSA alone, treatment with telavancin resulted in cure rates of 82% compared with 74% for vancomycin; this difference did not reach statistical significance but is clinically meaningful. In clinically evaluable patients with VAP, the cure rate was 80% for telavancin compared with 68% for vancomycin.

In November, telavancin received a favorable recommendation from the Anti-Infective Drugs Advisory Committee of the FDA with a vote of 21-5. The NDA was submitted for the indication of cSSSI. Astellas, who in-licensed the antibiotic from Theravance, is working closely with the company towards FDA approval. On the downside, Astellas has withdrawn its European marketing authorization application for telavancin, based on communications from the CHMP that the data submitted are insufficient to provide a proper benefit/risk assessment for the indication of complicated skin and soft tissue infections. The company plans to submit a new MAA with expanded clinical data, including data from hospital-acquired pneumonia phase III studies.