Terlipressin is an investigational product and its safety and effectiveness have not yet been established by the
As previously announced, the Phase 3 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
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).
“The durability of HRS reversal with terlipressin in CONFIRM persisted to Day 30 without the need for RRT. This is a clinically significant observation, as RRT poses many challenges for patients with advanced cirrhosis,” said lead author
The incidence of adverse events (AEs) of any severity were similar in both groups (88.0 percent of the terlipressin group and 88.9 percent of the placebo group). The most commonly reported AEs in the overall study population were abdominal pain, nausea, diarrhea, hepatic encephalopathy and dyspnea. Serious AEs (SAEs) were reported in 65.0 percent (n=130) of the terlipressin group and 60.6 percent (n=60) of the placebo group. The most commonly reported SAEs included hepatobiliary disorders, respiratory disorders and gastrointestinal disorders.4
At present, there are no drug therapies approved for the treatment of HRS-1 in the
Terlipressin is approved in many countries outside the
“The CONFIRM results provide meaningful insight into the management of HRS-1 in clinical practice, and we are pleased to be able to share these important data broadly with the healthcare community,” said
About the Pivotal Phase 3 CONFIRM Study (multi-center, randomized, placebo-controlled, double-blind trial in the
- The trial was designed to confirm efficacy and safety of terlipressin for the treatment of HRS-1.
- In the 35-month study period, 300 patients from the
U.S.(89.0 percent) and Canada(11.0 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. 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 61.0 percent were categorized as Child-
Pugh Class C.
- Eligibility criteria included adults with liver cirrhosis and ascites with rapidly worsening renal function and no response to diuretic withdrawal or volume expansion with albumin.
- Subjects were randomized in a 2:1 ratio to receive terlipressin plus albumin (n=199) or placebo plus albumin (n=101).
- The primary endpoint of Verified HRS Reversal evaluated renal function improvement, avoidance of dialysis and short-term survival.
Terlipressin is a potent vasopressin analogue selective for V1 receptors being investigated for the treatment of HRS-1 in the
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CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements with regard to terlipressin, including with regard to interactions with regulators as well as its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.
Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2021 Mallinckrodt. US-2000496 02/21
1 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed January 12, 2021.
2 Colle I and Laterre PF. Hepatorenal syndrome: the clinical impact of vasoactive therapy. Expert Review of Gastroenterology & Hepatology. (2018) 12:2, 173-188, DOI: 10.1080/17474124.2018.1417034.
3 Gines P, Sola E, Angeli P, et al. Hepatorenal syndrome. Nature Reviews. (2018) 4:23.
4 Wong F, Pappas C, Curry M, et al. Terlipressin plus albumin for the treatment of hepatorenal syndrome type 1.
5 Boyer TD, Medicis JJ, Pappas SC, et al. A randomized, placebo-controlled, double-blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin: the REVERSE trial design. Open Access Journal of Clinical Trials 2012:4. https://www.dovepress.com/a-randomized-placebo-controlled-double-blind-study-to-confirm-the-reve-peer-reviewed-article-OAJCT.
6 C Pant, B S Jani, M Desai, A Deshpande,
7 United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed January 12, 2021.
8 De Franchis R. Evolving Consensus in Portal Hypertension Report of the
9 Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews. 2003;1. doi: 10.1002/14651858.CD002147.
10 European Association for the Study of the Liver (EASL). Clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460.
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