Telavancin: TD 6424, TD-6424

Telavancin [TD-6424, ARBELIC] is an injectable, bactericidal lipoglycopeptide antibacterial that is in clinical development with Theravance (formerly Advanced Medicine) in the US. Telavancin, which was discovered by Theravance through the application of multivalent drug design, has a broad spectrum of activity against Gram-positive pathogens. Telavancin is currently in phase III development for complicated skin and soft tissue infections (including those caused by methicilin-resistant Staphylococcus aureus [MRSA]), nosocomial pneumonia, as well as other Gram-positive pathogens. The antibacterial effects of telavancin are mediated through multiple mechanisms, including inhibition of cell wall (peptidoglycan) synthesis. The drug also produces changes in bacterial cell membrane permeability. The multiple mechanisms of action may be responsible for the low frequency of spontaneous resistance to telavancin. Theravance and Astellas Pharma entered into a licensing agreement for telavancin in November 2005. The two companies will collaborate for the development and commercialisation of the antibacterial agent worldwide, except Japan. Under the terms of the agreement, Astellas will make a 65 million US dollars up-front payment and royalties on global sales to Theravance; in addition, Theravance is eligible to receive 156 million US dollars in clinical and regulatory milestones payments, including 136 million US dollars for completing enrollment, filling and approval of ongoing phase III programmes, and 20 million US dollars if phase III data indicate telavancin's superiority over vancomycin for the treatment of MRSA. Theravance will continue to explore partnering opportunities in the Japanese market. Telavancin was granted fast-track status by the US FDA in March 2005 for the treatment of complicated skin and skin structure infections (cSSSIs), as well as hospital-acquired pneumonia (nosocomial pneumonia). The compound is currently in phase III trials for these indications in the US. Theravance has also conducted two randomised, double-blind phase II trials (FAST and FAST 2) of telavancin in patients with cSSSIs caused by Gram-positive bacteria, in which telavancin (7 or 10 mg/kg) was compared with standard vancomycin therapy. Results showed that while telavancin was comparable to standard therapy overall, telavancin was associated with superior MRSA eradication rates.