Mallinckrodt announces New England Journal of Medicine publication of results from its hase III CONFIRM study of terlipressin in patients with hepatorenal syndrome Type 1 (HRS-1).

Mallinckrodt Plc, announced publication of results from its pivotal Phase III CONFIRM study to assess the efficacy and safety of its investigational agent terlipressin in adults with hepatorenal syndrome type 1 (HRS-1) . HRS-1 is an acute and life-threatening syndrome involving acute kidney failure in patients with cirrhosis, and has a median survival time of approximately two weeks and greater than 80 percent mortality within three months if left untreated. The study was posted online ahead of print publication in the New England Journal Of Medicine. As previously announced, the Phase III CONFIRM study met its primary endpoint of Verified HRS Reversal, which is defined as renal function improvement, avoidance of dialysis and short-term survival. The main objective of the CONFIRM study was to assess the efficacy and safety of terlipressin, together with albumin, versus placebo in adults in the U.S. and Canada with cirrhosis and HRS-1. The trial met three of the four pre-specified secondary endpoints of the study including HRS reversal, HRS reversal without renal replacement therapy (RRT) by Day 30 and HRS reversal in the systemic inflammatory response syndrome (SIRS) subgroup. The fourth pre-specified secondary endpoint of Verified HRS Reversal without HRS recurrence by Day 30 was 50 percent greater in the terlipressin group but did not reach statistical significance. Initial results were announced during a late-breaking abstract presentation on November 11, 2019 at The Liver Meeting, the annual meeting of the American Association For The Study Of Liver Diseases (AASLD). In another pre-specified endpoint, avoidance of RRT, terlipressin treated subjects (n=199) showed a significantly lower incidence during the treatment period and a lower incidence at all follow-up assessments through Day 90 versus patients with placebo (n=101).4 This is clinically significant because RRT can increase complications in HRS-1 due to the underlying cirrhosis (i.e. coagulopathy, low blood pressure). See- "Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome"_Florence Wong, M.B., B.S., M.D., S. Chris Pappas, M.D., J.D., Michael P. Curry, M.D., et al., for the CONFIRM Study Investigators.March 4, 2021 .N Engl J Med 2021; 384:818-828 . DOI: 10.1056/NEJMoa2008290.