Mallinckrodt plc presents positive phase 3 results from its confirm study of terlipressin in patients with hepatorenal syndrome type 1 (hrs-1) at the liver meeting 2019

Mallinckrodt plc announced results from its pivotal phase 3 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 people with cirrhosis. results were reported during a late-breaking abstract presentation today at the liver meeting® 2019, the annual meeting of the american association for the study of liver diseases (aasld), in boston. the confirm abstract was also selected by aasld for inclusion in its prestigious "best of the liver meeting" educational program in the portal hypertension/cirrhosis category. in the 35-month study period, 300 patients from the u.s. (89%) and canada (11%) participated in the largest-ever prospective, multi-center randomized controlled clinical trial in hrs-1. patients in the study were critically ill, as indicated by assessments of their liver and kidney function at the start of the trial. patients in the trial had a mean model for end-stage liver disease (meld) score of 33; a mean serum creatinine (scr) level of 3.5 mg/dl; and 61% were categorized as child-pugh class c. the study met its primary endpoint of verified hrs reversal (vhrsr), which is defined as renal function improvement, avoidance of dialysis and short-term survival. 29.1% (58/199) of patients administered terlipressin plus albumin achieved verified hrs reversal versus 15.8% (16/101) on placebo plus albumin (p=0.012). in order to achieve verified hrs reversal, patients had to have two consecutive scr values =1.5 mg/dl, at least two hours apart by day 14 or hospital discharge, and be alive without intervening renal replacement therapy (rrt) for at least 10 days following discharge or treatment. confirm study key findings: the study met its primary endpoint of verified hrs reversal, defined as two consecutive scr values =1.5 mg/dl, at least two hours apart by day 14 or discharge, with subjects alive without rrt for at least 10 days after the second scr =1.5 mg/dl; 29.1% (n=58) of patients treated with terlipressin plus albumin compared to 15.8% (n=16) of patients treated with placebo plus albumin (p=0.012) achieved verified hrs reversal. the four pre-specified secondary endpoints of the study were: hrs reversal: 36.2% (n=72) of patients in the terlipressin group demonstrated hrs reversal, defined as the percentage age of participants with a scr value no more than 1.5 mg/dl by day 14 or discharge versus 16.8% (n=17) on placebo (p<0.001); durability of/maintaining hrs reversal: 31.7% of patients receiving terlipressin (n=63) maintained hrs reversal without rrt/dialysis up to day 30 versus 15.8% (n=16) in the placebo group (p<0.003). hrs reversal in the systemic inflammatory response syndrome (sirs) subgroup: 33.3% (28/84) of patients with sirs in the terlipressin arm achieved verified hrs reversal versus 6.3% (3/48) in the placebo arm (p<0.001). verified hrs reversal without hrs recurrence by day 30: 24.1% (n=48) of patients on terlipressin and 15.8% (n=16) of patients in the placebo group (p=0.092) achieved verified hrs reversal without recurrence by day 30. adverse events (aes) were similar in both groups. serious aes were reported in 65% (n=130) of subjects in the terlipressin group and 60.6% (n=60) in the placebo group. the most commonly reported serious aes included respiratory failure, which occurred in 10% of the terlipressin group and 3% of the placebo group; and abdominal pain, which occurred in 5% of the terlipressin group and 1% of the placebo group. the most commonly reported aes included abdominal pain, which occurred in 19.5% of the terlipressin group and 6.1% of the placebo group; and nausea, which occurred in 16% of the terlipressin group and 10.1% of the placebo group. ischemia-associated aes occurred in 4.5% of the terlipressin group and 0% in the placebo group. no new or unexpected aes were reported.
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