Terlipressin is an investigational product and its safety and effectiveness have not yet been established by the
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
Terlipressin is approved in many countries outside
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
"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
This study was funded by Mallinckrodt.
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 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.
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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. © 2020 Mallinckrodt. US-2000454 11/20
1 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed
2 Moore K, Jamil K, Verleger K, Kelkar S, Kebede N et al. Predictors of response to terlipressin in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI): A multicenter study. Poster presented at: The Liver Meeting Digital Experience;
3 De Franchis R. Evolving Consensus in Portal Hypertension Report of the
4 Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews. 2003;1. doi: 10.1002/14651858.CD002147.
5 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.
6 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.
7 Gines P, Sola E, Angeli P, et al. Hepatorenal syndrome. Nature Reviews. (2018) 4:23.
8 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.
9 C Pant, B S Jani, M Desai, A Deshpande,
10 United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed November 3, 2020.
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