Superior efficacy of helicase-primase inhibitor BAY 57-1293 for herpes infection and latency in the guinea pig model of human genital herpes disease.

The efficacy of BAY 57-1293, a novel non-nucleosidic inhibitor of herpes simplex virus 1 and 2 (HSV-1 and HSV-2), bovine herpesvirus and pseudorabies virus, was studied in the guinea pig model of genital herpes in comparison with the licensed drug valaciclovir (Valtrex). Early therapy with BAY 57-1293 almost completely suppressed the symptoms of acute HSV-2 infection, and reduced virus shedding and viral load in the sacral dorsal root ganglia by up to three orders of magnitude, resulting in decreased latency and a greatly diminished frequency of subsequent recurrent episodes. In contrast, valaciclovir showed only moderate effects in this set of experiments. When treatment was initiated late during the course of disease after symptoms were apparent, that is, a setting closer to most clinical situations, the efficacy of therapy with BAY 57-1293 was even more pronounced. Compared with valaciclovir, BAY 57-1293 halved the time necessary for complete healing. Moreover, the onset of action was fast, so that only very few animals developed new lesions after treatment commenced. Finally, in a study addressing the treatment of recurrent disease in animals whose primary infection had remained untreated BAY 57-1293 was efficient in suppressing the episodes. In summary, superior potency and efficacy of BAY 57-1293 over standard treatment with valaciclovir was demonstrated in relevant animal models of human genital herpes disease in terms of abrogating an HSV infection, reducing latency and the frequency of subsequent recurrences. Furthermore, BAY 57-1293 shortens the time to healing even if initiation of therapy is delayed.

Antibacterial research and development in the 21(st) Century--an industry perspective of the challenges.

The continued evolution of resistance to antibiotics has led to wide ranging consultation at National and International levels as to how to address this issue. In addition to attempting to limit the spread of resistance there is growing consensus that a cornerstone requirement is the development of new antibiotics to help redress the balance of resistance versus available antibiotics. The availability of new technologies such as genomics has opened up new approaches for antibacterial research. It would appear that from an industry perspective, the research and development of antibiotics should be an attractive option. However, this is not the current perception at the majority of large pharmaceutical companies. In addition, the perceived failure of new technologies to create another golden age of new antibacterial classes has led many companies to prioritise other areas of research and, in some cases, to exit antibacterial research. In response, a plethora of small biotech companies have emerged with an interest in antibacterial discovery and large pharmaceutical companies may look to these as a source of development candidates although, to date, these have contributed a very low number of truly novel antibiotic lead compounds. As a reaction to these changes several initiatives are ongoing to examine ways to incentivise antibacterial research and development and ensure a healthy pipeline of compounds in the 21st Century.