Phase III CONFIRM study of Variquel meets primary endpoint in hepatorenal syndrome type 1.- Mallinckrodt

Mallinckrodt announced results from its pivotal Phase III CONFIRM study to assess the efficacy and safety of its investigational agent Variquel (terlipressin) in adults with hepatorenal syndrome type 1 (HRS-1). In the 35-month study period, 300 patients from the U.S. (89 percent) and Canada (11 percent) 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. P

atients 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 percent 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 percent (58/199) of patients administered terlipressin plus albumin achieved Verified HRS Reversal versus 15.8 percent (16/101) on placebo plus albumin (p=0.012). In order to achieve Verified HRS Reversal, patients had to have two consecutive SCr values less or equal to 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.

HRS-1 is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis.1 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.

Comment: HRS-1 has a median survival time of less than two weeks and greater than 80 percent mortality within three months if left untreated. At present, there are no approved drug therapies for HRS-1 in the U.S. or Canada. HRS-1 is estimated to affect between 30,000 and 40,000 patients in the U.S. annually. Terlipressin is an investigational product and its safety and effectiveness have not yet been established by the U.S. FDA or Health Canada. The company plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) in the first half of 2020.