Talactoferrin Shows Promise for Treatment of Severe Sepsis

Jeffrey Crawford, MD

The investigational oral agent talactoferrin alfa reduces the risk of death in patients being treated in the intensive care unit for severe sepsis, according to data from a phase II study presented at the 14th World Conference on Lung Cancer in Amsterdam, The Netherlands. The researchers said that the findings may be particularly relevant to cancer patients.

Results of a modified intent-totreat analysis (ITT) showed a 28-day mortality rate of 26.6% in severely septic patients who received placebo plus best supportive care versus 14.4% in patients who received talactoferrin plus best supportive care (two-tailed; P = .052); this translates into a 46.5% relative reduction in 28-day mortality with talactoferrin.

Talactoferrin is an investigational oral immunotherapy. The compound has also shown activity in non—small cell lung cancer as monotherapy in the second- and third-line setting and when added to a first-line chemotherapy doublet.

“The study met the primary endpoint of reducing 28-day mortality in the modified ITT population, which is important for cancer patients, who represent a population that is at increased risk of sepsis because their immune systems are often depressed by the treatments they receive,” said Jeffrey Crawford, MD, professor of medicine at Duke University Medical Center in Durham, North Carolina, who presented the data.

“Cancer patients also have a higher risk of infection due to frequent hospitalization, surgeries, and weakness due to illness,” he added.

For the study, 190 patients who had at least one organ dysfunction due to sepsis during the prior 24 hours and who had known or suspected infection with at least 2 of 4 systemic inflammatory response criteria were randomized to talactoferrin 1.5 g or placebo enterally every 8 hours for a maximum of 28 days in addition to standard best supportive care, including (at the doctor’s discretion) activated drotrecogin alfa.

The analysis showed that the mortality rate was consistently lower in the talactoferrin arm across infection sites (including lung, blood, urinary, and skin infections), with the exception of intra-abdominal infections. A consistent reduction in mortality also occurred in patients with a single isolate and polymicrobial isolates. Talactoferrin was well tolerated.

Crawford said that a phase II/III study with talactoferrin in patients with sepsis is currently underway.