3Rs for innovating novel antibiotics: sharing resources, risks, and rewards.

The dearth of novel antibiotics poses challenges to the treatment of bacterial infection and points to shortcomings in the system of pharmaceutical innovation. Increasing bacterial resistance to existing antibiotics causes substantial morbidity and mortality and threatens society’s ability to realise benefits from modern medical advances. Access to effective antibiotics is essential to treating the unavoidable infections that come with cancer chemotherapy, organ transplantation, or the care of premature babies. Yet studies have repeatedly confirmed the faltering research pipeline for novel antibiotics and cited the exit of major pharmaceutical firms from this therapeutic area. In the publicly disclosed pipelines of the top 15 drug companies, only five drug candidates, or 1.6% of the pipeline, were antibiotics. A more comprehensive search of two commercial databases also turned up few novel antibacterial drug candidates.Of the 15 candidates identified that could be administered systemically, only four were active against Gram negative bacteria, two of which acted on new targets; none of the four had a novel mechanism of action. With few promising drug candidates in sight, the near term prospects of new antibiotics are dismal. The bottlenecks in bringing a novel antibiotic to market span from discovery to delivery (fig 1⇓). Upstream in the research and development pipeline, concerns have surfaced over identification of leads and medicinal chemistry. Especially critical is the step between preclinical and clinical development (the “valley of death”). Drug companies have been hesitant to take compounds into large and costly clinical programmes because of the uncertain return on investment and academic researchers and smaller companies find it difficult to get venture capital for clinical research. Downstream, concerns over the regulatory approval process have stirred debate, and financing research and development may also pose barriers. Drug companies have to see that their expected returns will exceed the costs of research and development. But compared with other therapeutic categories, the economic value of antibiotics to pharmaceutical firms is considerably lower. Research into antibiotics therefore often loses out to potentially more lucrative health technologies. Possible interventions to improve the pipeline have been identified. 6 But identifying which is the inspired solution is not easy. Nor is there likely to be a single solution. Effective solutions are likely to include sharing the three Rs—resources, risks, and rewards.. Sharing resources