Mallinckrodt plc, a global biopharmaceutical company, today announced results from a post hoc analysis of a retrospective chart review study of terlipressin in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI) conducted in 26 hospitals in the United Kingdom. HRS-AKI, also known as HRS-1, is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis.1 Results were presented during a poster presentation at The Liver Meeting Digital Experience, the annual meeting of the American Association for the Study of Liver Diseases (AASLD). The poster can be accessed here on the company's website.
Terlipressin is an investigational product and its safety and effectiveness have not yet been established by the U.S. Food and Drug Administration.
The retrospective chart review study included 250 hospitalized adult patients from 26 centers in the U.K. with a diagnosis of HRS-AKI who received terlipressin or other vasopressors. The majority of patients were treated with terlipressin (n=203) and were evenly distributed by baseline AKI severity: mild, 33 percent (SCr <2.25 mg/dL); moderate, 36 percent (SCr ≥2.25 mg/dL and <3.5 mg/dL); severe, 31 percent (SCr ≥3.5 mg/dL). The overall response rate among patients treated with terlipressin, including complete responses (SCr ≤1.5 mg/dL) and partial responses (SCr reduction ≥20 percent but SCr >1.5 mg/dL), was 73 percent and differed between the mild and moderate (79 percent and 78 percent) groups compared to the severe group (60 percent). The retrospective chart review study identified absence of a precipitating event, concomitant use of albumin and mild or moderate baseline AKI severity as predictors of overall response. Presence of encephalopathy was the only predictor of mortality (hazard ratio, 2.77; 95 percent confidence interval, 1.56 to 4.92) identified by the study.2
Other outcomes included need for dialysis, mortality, liver transplantation and adverse event rates. The limitations of this post hoc analysis of a retrospective chart review include a more heterogeneous HRS population than those in randomized clinical trials, sampling bias from conveniently selected enters, potential selection bias towards patients with known outcomes to the providers and under reporting of less severe adverse events.
"As a physician treating patients with difficult to treat conditions like HRS-1, it's important to continue to build on decades of research of investigational products like terlipressin that can advance our scientific understanding of potential treatment options for these very sick patients," said Kevin Moore, M.D., UCL Institute of Liver and Digestive Health, Royal Free Hospital, University College London.
Terlipressin is approved in many countries outside the United States, where it has been a standard of care for decades in the treatment of patients with HRS-1.3,4 Terlipressin, together with albumin, is currently the standard of care for HRS-1 in countries where it is available.5
HRS-1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months if left untreated.6,7 At present, there are no drug therapies approved for the treatment of HRS-1 in the U.S. or Canada.8 HRS-1 is estimated to affect between 30,000 and 40,000 patients in the U.S. annually.9,10
"Mallinckrodt remains committed to furthering our understanding of HRS-1 and the potential of terlipressin to address HRS-1, a disease that is often a challenge to effectively diagnose," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "The results from this U.K. study add to the extensive knowledge and data of the investigational product in the U.S."