– Pooled analysis from Phase 3 clinical trials
highlights liver transplant rates in adult patients with HRS with
rapid reduction in kidney function treated with
TERLIVAZ1 –
DUBLIN, Oct. 26,
2024 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical
company, today announced a poster presentation on
TERLIVAZ® (terlipressin) for injection in patients with
hepatorenal syndrome (HRS) with rapid reduction in kidney
function1 at Kidney Week 2024, the annual meeting of the
American Society of Nephrology (ASN) taking place in San Diego from October
23-27, 2024.
TERLIVAZ is the first and only FDA-approved product indicated to
improve kidney function in adults with HRS with rapid reduction in
kidney function,1 an acute and life-threatening
condition requiring hospitalization.2 HRS involving
rapid reduction in kidney function1 is estimated to
affect more than 42,000 Americans annually, approximately 0.01% of
the U.S. population,3 making it a very rare condition;
and rates of hospitalizations are increasing.4
Please see Limitation of Use and Important Safety
Information, including Boxed Warning, below.
The poster presentation highlights a pooled analysis of data
from the CONFIRM and REVERSE Phase 3 placebo-controlled trials of
TERLIVAZ.5 The analysis examined the rates of
hepatorenal syndrome-acute kidney injury (HRS-AKI) reversal, renal
replacement therapy (RRT), and liver transplant (LT) among a
subpopulation of patients listed for LT at baseline who met FDA
label guidelines for treatment with TERLIVAZ (SCr <5 mg/dL, ACLF
grade 0–2, and MELD score <35).5 In this patient
subpopulation, treatment with TERLIVAZ increased the rate of
HRS-AKI reversal and reduced the need for RRT at all time points
assessed.5 The increase in HRS-AKI reversal with
TERLIVAZ did not negatively impact the LT rate in patients listed
for LT at baseline.5
- The rate of HRS-AKI reversal was 43% in the TERLIVAZ group
(n=53) and 20% in the placebo group (n=35).5
- The rate of RRT in the TERLIVAZ and placebo groups was 28% and
46% by Day 30; 32% and 54% by Day 60; and 36% and 54% by Day 90,
respectively.5
- The LT rate was similar in the TERLIVAZ and placebo groups at
all time points assessed: 53% and 51% by Day 30; 66% and 57% by Day
60; and 66% and 63% by Day 90, respectively.5
The limitations of this study include, but are not limited to,
small sample sizes, variables in methodology, and possible errors
and omissions within the data sets.5
"This analysis of data from our Phase 3 trials furthers our
understanding of the appropriate patient subpopulations and the
potential impact of treatment on liver transplantation rates," said
Peter Richardson, MRCP (UK),
Executive Vice President & Chief Scientific Officer. "For
these critically ill patients with HRS-AKI, a liver transplant is
the definitive treatment, and we know there are significant
challenges associated with RRT; which makes continued research
important."
This study was sponsored by Mallinckrodt Pharmaceuticals.
Presentation details can be found below:
Poster #PO0102-2: Hepatorenal syndrome-acute kidney injury
reversal and liver transplant rates in patients treated with
terlipressin5
- Presenter: Justin
Belcher
- Session Type: Poster Presentation
- Session Title: AKI: Clinical, Outcomes, and Trials -
Management
- Session Date and Time: Saturday, October 26, 2024; 10:00
a.m. – 12:00 p.m. PT
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%.
Contraindications
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.
Adverse Reactions
- 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.
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.2 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.2 HRS involving rapid reduction in kidney
function1 is estimated to affect more than 42,000
Americans annually, approximately 0.01% of the U.S.
population,3 making it a very rare condition; and rates
of HRS hospitalizations are increasing.4 If left
untreated, HRS with rapid reduction in kidney function1
has a median survival time of less than two weeks and greater than
80 percent mortality within three months.6
ABOUT MALLINCKRODT
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; 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.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
STATEMENTS
This release contains forward-looking statements,
including with regard to TERLIVAZ®, its potential to
improve health and treatment outcomes, 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: the effects of Mallinckrodt's recent emergence from bankruptcy;
satisfaction of, and compliance with, 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 or
adverse side effects or adverse reactions associated with TERLIVAZ;
and other risks identified and described in more detail in the
"Risk Factors" and "Management's Discussion and Analysis of
Financial Condition and Results of Operations" sections of
Mallinckrodt's most recent Annual
Report on Form 10-K, Quarterly Reports on Form 10-Q, 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.
CONTACT
Media Inquiries
Green Room Communications
908-577-4531
mediainquiries@grcomms.com
Investor Relations
Derek
Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com
Mallinckrodt, the "M" brand mark,
TERLIVAZ, and the Mallinckrodt Pharmaceuticals logo are
trademarks of a Mallinckrodt company. Other brands are
trademarks of a Mallinckrodt company or their respective
owners.
©2024 Mallinckrodt.
US-2400773 10/24
References
1 TERLIVAZ® (terlipressin) for Injection.
Prescribing Information. Mallinckrodt Hospital Products Inc.
2023.
2 National Organization for Rare Disorders. Hepatorenal
Syndrome. Available at:
https://rarediseases.org/rare-diseases/hepatorenal-syndrome/.
Accessed October 2024.
3 United States Census Bureau: Quick Facts. Available
at: https://www.census.gov/quickfacts/fact/table/US/PST045218.
Accessed October 2024.
4 Singh J., Dahiya D.S., Kichloo A., et al. Hepatorenal
Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals
of Med. 2021;53:1. 2018-2024 doi.org/10/1080/07853890.
5 Belcher J.M., Regner K.R., Mujtaba M.A., et al.
Hepatorenal syndrome-acute kidney injury reversal and liver
transplant rates in patients treated with terlipressin. Abstract
to be presented at the American Society of
Nephrology (ASN) 2024 Annual meeting. October 2024.
6 Flamm, S.L., Brown, K., Wadei, H.M., et al. The
Current Management of Hepatorenal Syndrome–Acute Kidney Injury in
the United States and the
Potential of Terlipressin. Liver Transpl. 2021;27:1191-1202.
https://doi.org/10.1002/lt.26072.
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SOURCE Mallinckrodt plc