Mallinckrodt Presents Clinical Data for TERLIVAZ® (terlipressin) for Injection in Adults with Hepatorenal Syndrome (HRS) at Digestive Disease Week (DDW) 2023
– Findings from two clinical study presentations in adults with HRS involving rapid reduction in kidney function1 provide insight into the appropriate use of terlipressin for the care of critically ill patients2,3 –
TERLIVAZ is the first and only FDA-approved product indicated for the treatment of adults with HRS involving rapid reduction in kidney function,1 an acute and life-threatening condition requiring hospitalization.4 Terlipressin is recommended by the
Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.
Presented by Jasmohan S. Bajaj,
The pooled safety population included 598 patients, of which 349 received terlipressin and 249 received placebo. The incidence of episodes of bradycardia was higher in terlipressin-treated patients (6.3%; n=22) compared with placebo-treated patients (0.8%; n=2; P<0.001), and none of these episodes were considered serious. Bradycardia was classified as severe per investigator assessment in 68.2% (n=15/22) of patients in the terlipressin group and in 100% (n=2/2) of patients in the placebo group, and most patients did not require a change in treatment dose (terlipressin: 72.7%; n=16/22 vs. placebo: 50%; n=1/2; P=0.507). One patient treated with terlipressin had a dose interruption, and there were no treatment discontinuations.2
Further, no differences were observed between treatment groups (terlipressin: arrhythmia [0%, n=0/349,]; nodal arrhythmia [0%, n=0/349]; ventricular fibrillation [0%, n=0/349] vs. placebo: arrhythmia [0.8%, n=2/249, P=0.173]; nodal arrhythmia [0.4%, n= 1/249, P=0.416]; ventricular fibrillation [0.4%, n=1/249, P=0.416]. Atrial fibrillation was the most reported arrhythmia across the pooled safety population (total: 4.0%, n=24/598; terlipressin: 3.7%, n=13/349; placebo: 4.4%, n=11/249; P=0.678).2
To be presented by
"The findings of this subgroup analysis of the CONFIRM Phase III study build upon the growing body of evidence supporting the use of TERLIVAZ® (terlipressin) for injection as a treatment option among critical care patients with HRS, including its therapeutic ability to drive meaningful clinical outcomes for a significant population of patients with comorbid conditions, such as alcoholic hepatitis,3" added
In CONFIRM (n=300), 41% (81/199) of patients in the terlipressin group and 39% (39/101) of the patients in the placebo group had AH at baseline. In the subgroup of patients with AH (n=120), the median Maddrey discriminant function score was similar across treatment groups (terlipressin: 96.9 vs. placebo: 97.7; P=0.681). Verified HRS reversal was achieved in 30.9% (n=25/81) of patients in the terlipressin group vs. 7.7% (n=3/39) in the placebo group (P=0.005).3
Additionally, admission to the ICU was similar for patients in the terlipressin and placebo groups (17.3%, n=14 vs. 17.9%, n=7), whereas mean length of stay in the ICU was shorter for terlipressin (6.9 days) vs. the placebo group (12.4 days). There was a numerical decrease in RRT by Day 30 in the terlipressin group vs. the placebo group (21%, n=17 vs. 25.6%, n= 10).3
These studies were sponsored by Mallinckrodt Pharmaceuticals:
- Poster Su1535*: Low Incidence of Clinically Significant Bradycardia and Arrhythmia in Patients with Hepatorenal Syndrome Following Terlipressin Treatment: A Pooled Analysis of 3 North American Phase III Clinical Studies2
- Presenter: Jasmohan S. Bajaj,
School of Internal Medicine, Virginia Commonwealth University, Richmond, Va.
*Poster of Distinction
To be presented
- Oral Lecture 651: Clinical Responses to Terlipressin in the Subgroup of Patients with Hepatorenal Syndrome Further Compounded by Alcoholic Hepatitis: Analysis of the CONFIRM Phase III Study3
- Presenter: Kevin Korenblat,
Washington University School of Medicine, St. Louis, Mo.
Find more information on the Digestive Disease Week (DDW) 2023 Meeting website.
About Digestive Disease Week®
Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the
About Hepatorenal Syndrome (HRS)
Hepatorenal syndrome (HRS) involving rapid reduction in kidney function1 is an acute and life-threatening condition that occurs in people with advanced liver disease.4 HRS is classified into two distinct types – a rapidly progressive type that leads to acute renal failure where patients are typically hospitalized for their care and a more chronic type that progresses over weeks to months.4 HRS involving rapid reduction in kidney function1 is estimated to affect between 30,000 and 40,000 Americans annually.7,8 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.9
INDICATION AND LIMITATION OF USE
TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.
- Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.
IMPORTANT SAFETY INFORMATION
WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE
- TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ.
- Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%.
TERLIVAZ is contraindicated:
- In patients experiencing hypoxia or worsening respiratory symptoms.
- In patients with ongoing coronary, peripheral, or mesenteric ischemia.
Warnings and Precautions
- Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms.
Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure.
- Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks.
- Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions.
- Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus.
- The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.
Please click here to see full Prescribing Information, including Boxed Warning.
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company's Specialty Brands reportable segment's areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release contains forward-looking statements, including with regard to TERLIVAZ and 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
Senior Vice President,
Global Corporate Controller & Chief Investor Relations Officer
Vice President, Investor Relations
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.
©2023 Mallinckrodt. US-2300189 5/23
1 TERLIVAZ® (terlipressin) for injection. [Prescribing Information].
2 Bajaj JS, et al. Low Incidence of Clinically Significant Bradycardia and Arrhythmia in Patients with Hepatorenal Syndrome Following Terlipressin Treatment: A Pooled Analysis of 3 North American Phase III Clinical Studies. Abstract Presented at Digestive Disease Week (DDW) 2023.
3 Korenblat, K et al. Clinical Responses to Terlipressin in the Subgroup of Patients with Hepatorenal Syndrome Further Compounded by Alcoholic Hepatitis: Analysis of the CONFIRM Phase III Study. Abstract to be Presented at Digestive Disease Week (DDW) 2023.
4 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed April 18, 2023.
5 Biggins SW, Angeli P,
6 Bajaj JS, O'Leary JG, Lai JC, et al. Acute-on-chronic liver failure clinical guidelines. Am J Gastroenterol. 2022;1-28.
7 C Pant, B S Jani, M Desai, A Deshpande,
8 United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed April 18, 2023.
9 Flamm SL, Brown K, Wadei HM., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in
View original content to download multimedia:https://www.prnewswire.com/news-releases/mallinckrodt-presents-clinical-data-for-terlivaz-terlipressin-for-injection-in-adults-with-hepatorenal-syndrome-hrs-at-digestive-disease-week-ddw-2023-301811418.html