Sepsis, a complex and rapidly progressing disease with up to 80% associated mortality, presents major challenges with regard to its epidemiology, definition and management. Rising disease incidence has been fuelled by the growing number of surgical interventions and an increase in immunocompromization. Disease management is predominantly non-specific, relying on a range of interventions.

• Assessment of sepsis epidemiology, disease progression, and approaches to diagnosis and management
• In-depth case study of Xigris, the only sepsis-specific drug on the market
• Discussion of the challenges associated with the development of a sepsis drug and reasons for the failure of past R&D programs
• Overview of immunomodulators currently in clinical development for the treatment of the sepsis response

Sepsis is widely regarded as the most challenging problem in intensive care, a direct consequence of the complexity of the disease, its rapid progression and heterogeneity of the patient population. Current diagnostics fail to allow for rapid and accurate diagnosis.

The execution of more than 60 randomized trials involving more than 15,000 subjects and costing more than $1 billion has produced only one sepsis-specific drug, Eli Lilly's Xigris. However, due to the drug's high price point, the narrow label and its contraindications, Xigris has failed to meet expectations, with global 2005 sales totaling $214.6m.

Successful development of the sepsis pipeline might lead to the first new drug, Takeda's TAK-242, reaching the market in 2009. Due to the high level of redundancy regarding molecular mediators in the sepsis response, future approaches are likely to focus on intervening at multiple points in the sepsis cascade.

• Understand the challenges associated with the definition and epidemiology of sepsis, both of which impact on effective drug development
• Identify unmet needs in sepsis diagnosis and treatment
• Optimize R&D strategies for sepsis based on the analysis of past developmental failures