While Eli Lilly and Co. is setting standards for sepsis trial design and patient selection by being the first company to show a reduction in 28-day all cause mortality in a pivotal trial, its success may further complicate the field for other sepsis players.

Sepsis has long been a daunting indication for pharmaceutical and biotech companies, largely because it is a complex syndrome associated with many underlying disorders. Due to the 28-day mortality endpoint the FDA has chosen to accept for sepsis trials, one major challenge lies in selecting a patient population in which the underlying disease pathology does not confound detection of a study drug effect.

While the last decade has seen an evolution in sepsis trials, including the adoption of scoring systems to stratify patients for the purpose of comparing more similar patient groups, the troublesome 28-day all cause mortality endpoint has not budged.

LLY (Indianapolis, Ind.) appears to have finally cleared that hurdle, and other sepsis companies are quick to note that their trial design is very similar to the pharma company's. But while that design may work now, if Xigris (formerly Zovant) is approved, it will complicate the scene by forcing trials to use an active product in control patients.

Endpoint enigma

While the 28-day endpoint has been a stumbling block for companies, the FDA has chosen it because it is a simple measure of patient benefit for a very complex disorder.