Sepsis and Septicemia

March 15, 2010

AM-Pharma issued positive results from a phase II trial of Alkaline Phosphatase for acute kidney injury. This double blind, placebo controlled, study enrolled 36 subjects with acute kidney injury secondary to sepsis. The subjects received Alkaline Phosphatase intravenously for 48 hours and were followed for 28 days. A composite analysis of all primary renal function efficacy parameters, creatinine clearance, serum creatinine and dialysis requirement showed statistically significant improvement compared to placebo (p≡0.005). Renal creatinine clearance improved more than twice as fast in the treated group during the first 7 days, (p<0.02) resulting in normalization of creatinine clearance for the rest of the 28 days, compared to the placebo group, where creatinine clearance remained impaired (p<0.02). There was a reduction of dialysis requirement after treatment with Alkaline Phosphatase compared to placebo (means: 10 hours versus 53 hours, p≡0.08). Secondary endpoints were also reached with significance. Treatment with Alkaline Phosphatase resulted in shorter stay in the intensive care unit (11 days versus 25 days; p<0.02) and in reduced need for mechanical ventilation (3.9 days versus 6.0 days; p<0.03).

March 8, 2010

Agennix reported positive long-term results from a phase II trial of oral talactoferrin alfa for the treatment of severe sepsis. This randomized, double-blind, placebo-controlled study enrolled 190 adult subjects with sepsis, and at least one organ dysfunction due to sepsis, in the US. The subjects received standard therapy and either talactoferrin alfa (1.5 g) or placebo three times a day for up to 28 days or until discharge from the intensive care unit, whichever occurred first. The primary endpoint, a reduction in 28-day all-cause mortality, was achieved. These data show that talactoferrin alfa also reduced all-cause mortality compared to placebo at three and six months. At three months, all-cause mortality was 29.3% in the placebo arm compared to 18.1% in the talactoferrin alfa arm (p%equiv;0.07). At six months, all-cause mortality was 35.2% in the placebo arm compared to 21.3% in the talactoferrin alfa arm (p≡0.04). The absolute reduction in six-month all-cause mortality of 14% was greater than the absolute reduction seen in 28-day all-cause mortality (which was 12%, from 26.6% in the placebo arm to 14.6% in the talactoferrin alfa arm).

September 5, 2005

Eisai reported results of a phase II trial of eritoran (E5564), their Toll-like receptor 4 antagonist for the treatment of severe sepsis. Results from the study yielded a positive trend towards decreasing mortality risk in the higher dose group to 22.4% (p=0.09), compared to 32.5% in the low dose group and 22.4% in the high dose group. Among the most high risk subjects, the high dose group had a mortality risk of 33.3% (p=0.07), and the low dose group had a risk of 37.9% (p=0.17), compared to 50.9% for placebo. This placebo-controlled study enrolled 293 patients in North America, who received either low dose (45 mg) or high dose (105 mg) eritoran or placebo twice daily for 6 days. Based on these results, the company announced plans to initiate phase III development of the drug in the US, Canada and Europe.

Emergent BioSolutions reported positive results of a phase II trial of their investigational oral typhoid vaccine, for the prevention of Salmonella typhi infections. Trial data indicated that a simple rapid dosing regimen did not negatively impact safety or immunogenicity levels, compared to an earlier regimen which required preloading with a bicarbonate buffer and a restricted reconstitution process. Both formulations were highly immunogenic, producing response deemed appropriate for clinical and commercial use. This open-label study enrolled 32 healthy subjects, who received single oral doses of either the older lyophilized formulation or Emergent's investigational vaccine. Following these results, the company announced plans to conduct additional phase II trials of the drug in Vietnam, prior to initiating phase III development.

NexMed has issued positive results of a phase I trial of their investigational antifungal nail lacquer NM100060 (NexACT terbinafine), for the treatment of onychomycosis (nail fungal infections). Pharmacokinetic data indicated that lacquer application of the drug produced peak plasma concentrations approximately 2500% less that a single oral dose of terbinafine, and comparable levels to an approved terbinafine cream. Target drug concentrations in nail clippings were achieved by mid-way through the treatment period. Safety data yielded no reported serious adverse events; the most common overall adverse event was minor local irritation. This double-blind, randomized, parallel-design, placebo controlled study enrolled 56 patients, who received treatment with NM100060, an approved 1% terbinafine cream, and and a single 250 mg terbinafine oral tablet. The company announced that they had initiated licensing discussions for the drug.

May 16, 2005

Inhibitex has issued positive results of a phase II trial of Aurexis for the treatment of Staphylococcus aureus bloodstream infections. The drug produced favorable results in the primary composite endpoint of mortality, relapse rate and infection-related complications, with one death and one relapse of infection in the Aurexis-plus-antibiotics group, vs. four deaths in the antibiotics-alone group. Pharmacokinetic data indicated that peak plasma concentrations did not reach levels previously attained in phase I healthy volunteer studies. The drug also demonstrated efficacy in several secondary endpoints, including reduction in incidence of sepsis severity progression, reduction in ICU time for during re-hospitalization, and reduced incidence of candida infection, vs. antibiotics alone. This randomized, placebo-controlled, double-blind study enrolled 60 patients with documented S. aureus bloodstream infections across 12 US sites. Subjects received Aurexis or placebo in combination with a standard course of antibiotics, and were followed for 56 days. The company announced plans to initiate a follow-up phase II study of the drug, based on these results.

May 28, 2002

Phase III data indicates that severe sepsis patients with pulmonary complications have a greater likelihood of survival with Eli Lilly's Xigris (drotrecogin alfa (activated)) treatment compared to treatment with standard care alone. The results were obtained from an analysis of two subsets in the PROWESS trial: subjects with severe sepsis who were on mechanical ventilation and severe sepsis subjects with chronic obstructive pulmonary disease (COPD). At day 28, a significantly higher number of Xigris-treated subjects were off ventilation (65.5%) compared to subjects receiving standard care (61%). Additionally, Xigris treatment significantly increased the survival rates for subjects independent of their ventilator status. Regarding COPD, an analysis of 408 severe sepsis subjects with COPD showed a 36% reduction in the risk of death with Xigris treatment compared to treatment with standard care.