BTA-9881

Human respiratory syncytial virus (hRSV) is a significant cause of respiratory illness in at-risk pediatric patients, immunocompromised adults and the elderly. No vaccine is currently available for the virus and treatment options are limited to the prophylactic treatment of at-risk infants with the mAb palivizumab (Synagis) and to therapeutic intervention with the nucleoside analog ribavirin (Rebetol). The clinical use of these agents is limited and a need exists for more effective treatment for the at-risk population. The merging of viral and cellular membranes is a crucial event in the hRSV life cycle that enables the virus to enter a host cell. The multistep fusion process is facilitated by the substantial refolding of a trimeric class I fusion protein (F protein), which is the main target of fusion inhibitors. Several small-molecule fusion inhibitors have been discovered, of which some have progressed significantly in the drug development process. BTA-9881 (Biota Holdings Ltd/MedImmune) and TMC-353121 (Johnson & Johnson) are the most advanced of this drug class. In addition, progress has been made in the development of next-generation antibodies such as motavizumab (Numax; MedImmune). This review will discuss the status and latest developments of compounds and antibodies that inhibit hRSV fusion.

Respiratory syncytial virus (RSV) is a very important pathogen worldwide. It occurs and recurs naturally throughout life. Both short and long term morbidity, and mortality are particularly significant for infants, especially those infants with underlying conditions and risk factors. Current treatment strategies for these patients (e.g Ribavirin) are limited but several new interventions (e.g. RSV604, BTA9881, ALN-RSV01) are under investigation. Several preventive agents and strategies have been developed (e.g. RSV-IGIV, palivizumab) and others are in the pipeline (e.g. motavizumab) and under development (e,g, Medi-557). In this article, we review the RSV clinical condition with a focus on the highest risk populations. In addition we review prevention and treatment strategies of the past, present and future for these high-risk patients. This review should provide a single valuable source of information to clinicians and investigators.