– Findings from a retrospective analysis suggest
that patients with baseline acute-on-chronic liver failure (ACLF)
grade ≤2 treated with TERLIVAZ® plus albumin had a
higher incidence of HRS reversal than those treated with placebo
plus albumin1 –
DUBLIN, Jan. 22,
2023 /PRNewswire/ -- Mallinckrodt plc (NYSE American: MNK), a
global specialty pharmaceutical company, today announced the
presentation of results from a retrospective analysis of three
North American-centric, Phase III, randomized, placebo-controlled
studies comparing the incidence of hepatorenal syndrome (HRS)
reversal with baseline acute-on-chronic liver failure (ACLF) grade
in adults with rapid reduction in kidney
function2 treated with TERLIVAZ® plus
albumin versus those treated with placebo plus albumin.
Investigators will present the findings during an oral presentation
at the SCCM 2023 Critical Care Congress on January 22, taking place in San Francisco, CA from January 21-24.
TERLIVAZ is the first and only FDA-approved product indicated
for the treatment of adults with HRS involving rapid reduction in
kidney function,2 an acute and life-threatening
condition requiring hospitalization.3 Terlipressin is
recommended by the American Association for the Study of Liver
Diseases (AASLD) guidance4 and the American College of
Gastroenterology (ACG) guidelines.5
Please see Limitation of Use and Important Safety
Information, including Boxed Warning, below.
The retrospective analysis used pooled data from the OT-0401,
REVERSE, and CONFIRM Phase III studies to compare the incidence of
HRS reversal by baseline ACLF grade in patients treated with
terlipressin plus albumin versus placebo plus albumin for up to 14
days. Severity of ACLF was graded according to the number of organ
failures (ACLF grade 0-1, grade 2, and grade 3). The incidence of
HRS reversal was defined as at least one serum creatinine value of
≤1.5 mg/dL while on treatment.1
"We're excited to share these data that not only provide
valuable insight into the association between baseline patient ACLF
grade and treatment response with TERLIVAZ, but also reinforce the
importance of early treatment intervention to help improve outcomes
for patients with HRS with rapid reduction in kidney
function,1,2" said Khurram
Jamil, Vice President, Hepatology, Clinical Development
& Critical Care. "In light of the recent FDA approval of
TERLIVAZ as the first and only treatment to improve kidney function
in adults with HRS with rapid reduction in kidney
function,2 we remain committed to addressing the
unmet needs of critically ill patient populations."
In the pooled analysis population (n=607), 278 patients had ACLF
grade 0-1 (terlipressin: n=164; placebo: n=114), 208 patients had
ACLF grade 2 (terlipressin: n=116; placebo: n=92), and 121 patients
had ACLF grade 3 (terlipressin: n=72; placebo: n=49). The incidence
of HRS reversal in terlipressin-treated patients decreased with
increasing ACLF grade (ACLF grade 0-1: 43% (n=71/164); ACLF grade
2: 28% (n=32/116); ACLF grade 3: 19% (n=14/72)), whereas HRS
reversal was similar across ACLF grades in placebo-treated patients
(ACLF grade 0-1: 18% (n=21/114); ACLF grade 2: 15% (n=14/92); ACLF
grade 3: 14% (n=7/49)).1
Additionally, a higher percentage of terlipressin-treated
patients with ACLF grade 0-1 or grade 2 achieved HRS reversal
compared with those in the respective placebo-treated groups (ACLF
grade 0-1: terlipressin 43% (n=71/164) vs placebo 18% (n=21/114);
ACLF grade 2: terlipressin 28% (n=32/116) vs placebo 15% (n=14/92))
(p<0.0001 and p=0.02, respectively). No differences in the
incidence of HRS reversal were observed between terlipressin- (19%;
n=14/72) and placebo- (14%; n=7/49) treated patients with ACLF
grade 3 (p=0.46).1
This study was sponsored by Mallinckrodt Pharmaceuticals:
Baseline ACLF Grade and Treatment Response to Terlipressin in
Patients with Hepatorenal Syndrome1
- Presenter: Ram Subramanian
- Presentation Date: January 22; 2:30PM PT
- Location: Exhibit Hall RST 8, Moscone Center South
Find more information on the Society of Critical Care Medicine's
(SCCM) 2023 Critical Care Congress Meeting website.
About Hepatorenal Syndrome (HRS)
Hepatorenal syndrome (HRS) involving rapid reduction in kidney
function2 is an acute and life-threatening condition
that occurs in people with advanced liver disease.3 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.3 HRS involving rapid reduction in
kidney function2 is estimated to affect between 30,000
and 40,000 Americans annually.6,7 If left untreated, HRS
with rapid reduction in kidney function has a median survival time
of approximately two weeks and greater than 80 percent mortality
within three months.8
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
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
- 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
TERLIVAZ is contraindicated:
- In patients experiencing hypoxia or worsening respiratory
- In patients with ongoing coronary, peripheral, or mesenteric
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
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
- 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 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
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Therefore, investors should look to the Investor Relations page of
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CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
This release includes forward-looking statements,
including with regard to TERLIVAZ, 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
Annual Report on Form 10-K for the fiscal year ended December 31, 2021, as updated by Mallinckrodt's Quarterly Reports on Form 10-Q for
the quarterly periods ended April 1,
July 1 and September 30, 2022 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.
Senior Vice President, Green Room Communications
Global Corporate Controller & Chief Investor Relations
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-2201162 1/23
1 Subramanian R. Baseline ACLF Grade and Treatment
Response to Terlipressin in Patients with Hepatorenal Syndrome.
Abstract. Presented at the Society of Critical Care Medicine
(SCCM) 2023 Critical Care Congress. January 2023.
2 TERLIVAZ® (terlipressin) for injection
[Prescribing Information]. Mallinckrodt Hospital Products Inc.
3 National Organization for Rare Disorders.
Hepatorenal Syndrome. Available at:
Accessed December 2, 2022.
4 Biggins SW, Angeli P, Garcia-Tsao G, et al.
Diagnosis, evaluation, and management of ascites, spontaneous
bacterial peritonitis and hepatorenal syndrome: 2021 practice
guidance by the American Association for the Study of Liver
Diseases. Hepatology. 2021;74(2):1014-1048.
5 Bajaj JS, O'Leary JG, Lai JC, et al.
Acute-on-chronic liver failure clinical guidelines. Am J
6 C Pant, B S Jani, M Desai, A Deshpande,
Prashant Pandya, Ryan Taylor, R Gilroy, M OIyaee. Heptorenal
syndrome in hospitalized patients with chronic liver disease:
results from the Nationwide Inpatient Sample 2002-2012. J of
Investig Med. 2016; 64:33-38.
7 United States Census Bureau: Quick Facts. Available
Accessed December 2, 2022.
8 Flamm SL, Brown K, Wadei HM., et al. The Current
Management of Hepatorenal Syndrome–Acute Kidney Injury in
the United States and the
Potential of Terlipressin. Liver Transpl.
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SOURCE Mallinckrodt plc