– Three posters highlight research
on outcomes of TERLIVAZ treatment in key subpopulations of adults
with HRS with rapid reduction in kidney
function1 –
DUBLIN, June 5, 2024
/PRNewswire/ -- Mallinckrodt plc, a
global specialty pharmaceutical company, today announced the
presentation of three posters on TERLIVAZ®
(terlipressin) for injection in patients with hepatorenal syndrome
(HRS) with rapid reduction in kidney function1 at the
2024 European Association for the Study of the Liver (EASL)
Congress taking place in Milan,
Italy from June 5-8, 2024.
The posters include a retrospective chart review that examined
the potential relationship of serum creatinine (SCr) levels and
treatment outcomes in support of earlier diagnosis;2
data analyzing clinical response to TERLIVAZ in HRS patients
with a mean arterial pressure (MAP) of <65 mm Hg;3
and the effect of TERLIVAZ on renal function among patients
with alcohol-associated hepatitis (AAH) and hepatorenal
syndrome-acute kidney injury (HRS-AKI) who had acute-on-chronic
liver failure (ACLF) grades 0–2.4
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.5 HRS involving
rapid reduction in kidney function1 is estimated to
affect more than 42,000 Americans annually and rates of
hospitalizations are increasing.6 Currently, TERLIVAZ is
only approved in the U.S.
Please see Limitation of Use and Important Safety
Information, including Boxed Warning, below.
"The posters being shared at EASL showcase the potential
benefits of treatment with TERLIVAZ in several patient
subpopulations where there is a significant need. We remain
steadfast in our dedication to furthering our knowledge on the
clinical outcomes for those affected by HRS and the role TERLIVAZ
treatment can play for appropriate patients," said Peter Richardson, MRCP (UK), Executive Vice
President & Chief Scientific Officer.
Poster #SAT-320: Early diagnosis and treatment with
terlipressin for adults with hepatorenal syndrome improves clinical
outcomes and reduces healthcare resource
utilization2
- Presenter: Dr. Juan F.
Gallegos-Orozco
- Session Type: Poster Presentation
- Session Title: Acute Liver Failure and Drug-Induced
Liver Injury
- Session Date and Time: Saturday, June 8, 2024; 10:00 –
10:08 a.m. CEST
This analysis used a decision-analytic model leveraging data
from the CONFIRM trial and a medical chart review study from the
United Kingdom to assess HRS
patients across SCr groups at the time of HRS diagnosis to evaluate
the potential impact of earlier HRS diagnosis and TERLIVAZ
treatment.2 The model assessed on-label treatment (SCr
levels <3 mg/dL or ≥3 to <5 mg/dL) with TERLIVAZ, and
excluded those with SCr levels ≥5 mg/dL or those with grade 3
ACLF.2
In this analysis, earlier HRS diagnosis and treatment with
TERLIVAZ was associated with a 3,040 greater HRS reversals, 960
fewer patients with renal replacement therapy (RRT) rate during
hospitalization, fewer intensive care unit days, and a shorter
overall length of hospitalization when compared to current clinical
practice.2 The analysis further showed that a reduction
in hospitalization could generate $11,504 savings/cost offset per person and a
total annual national savings of $460.2
million in the U.S. (based on 2023
U.S. dollars).2
Poster #SAT-076: Patients with hepatorenal syndrome and
lower baseline mean arterial pressure derive significant survival
benefit from treatment with terlipressin3
- Presenter: Dr. Paul Yien
Kwo
- Session Type: Poster Presentation
- Session Title: Cirrhosis and its complications: Portal
Hypertension
- Session Date and Time: Saturday, June 8, 2024; 8:30 a.m.
CEST
This analysis included pooled data from three Phase III,
placebo-controlled studies of TERLIVAZ in patients with HRS with
rapid reduction in kidney function and examined the clinical
response from patients with a baseline MAP of <65 mm Hg
(n=608).3 The rate of HRS reversal was 22.4% [11/49] in
the TERLIVAZ group and 5.9% [2/34] in the placebo group
(p=.041).3 The proportion of patients requiring RTT at
Day 30 was 28.6% [14/49] in the TERLIVAZ group and 47.1% [16/34] in
the placebo group (p=.085); at Day 60 was 30.6% [15/49] in the
TERLIVAZ group and 47.1% [16/34] in the placebo group (p=.128); and
at Day 90 was 34.7% [17/49] in the TERLIVAZ group and 47.1% [16/34]
in the placebo group (p=.258).3
Poster #THU-074: Effect of terlipressin on patients with
hepatorenal syndrome, alcohol-associated hepatitis, and
acute-on-chronic liver failure grade 0–24
- Session Type: Poster Session
- Session Title: Cirrhosis and its complications: ACLF and
Critical illness
- Session Date: Thursday, June 6, 2024
This analysis included pooled data from three Phase III studies
of TERLIVAZ to assess the effect of treatment on renal function
among the subpopulation of patients with AAH, HRS-AKI, and ACLF
grades 0–2 (n=141).4
Change in renal function, measured as least squares (LS) mean
changes in SCr from baseline to end of treatment (EOT) with and
without interaction between treatment and day were –0.98 mg/dL and
–1.02 mg/dL for the TERLIVAZ arms, and –0.35 mg/dL and –0.26 mg/dL
for the placebo arms, respectively.4 The difference in
LS mean change in SCr between the TERLIVAZ and placebo arms was
–0.64 mg/dL without interaction, and –0.76 mg/dL with interaction
between treatment and day (both p<.001).4
In the TERLIVAZ (n=84) and placebo (n=60) arms, the incidence of
HRS reversal (defined as at least 1
SCr value of ≤1.5 mg/dL while on treatment by Day 14 or
discharge) was 44.0% and 11.7% (p<.001),
respectively.4 Incidence of RRT on Days 30, 60, and 90
were 24% and 25%, 26% and 27%, and 26% and 27% (p>.800 for all),
respectively.4
Key Study Limitations
The safety and efficacy of TERLIVAZ within the study subgroups
assessed in SAT-320, THU-074, and SAT-076 have not been evaluated
by the FDA. The limitations of these studies include but are not
limited to small sample sizes, variables in methodology and
possible errors and omissions within the data sets.
These analyses were sponsored by Mallinckrodt
Pharmaceuticals.
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.5 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.5 HRS involving rapid reduction in kidney
function1 is estimated to affect more than 42,000
Americans annually and rates of HRS hospitalizations are
increasing.6 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.7
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 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-2400450
06/24
References
1 TERLIVAZ® (terlipressin) for Injection.
Prescribing Information. Mallinckrodt Hospital Products Inc.
2023.
2 Gallegos-Orozco JF, et al. Early Diagnosis and
Treatment with Terlipressin for Adults with Hepatorenal Syndrome
Improves Clinical Outcomes and Reduces Healthcare Resource
Utilization. Poster presentation to be shared at the 2024
European Association for the Study of the Liver (EASL)
Conference. June 2024.
3 Kwo P, et al. Patients with hepatorenal syndrome
and lower baseline mean arterial pressure derive significant
survival benefit from treatment with terlipressin. Poster
presentation to be shared at the 2024 European Association for the
Study of the Liver (EASL) Conference. June 2024.
4 Moore K, et al. Effect of terlipressin on
patients with hepatorenal syndrome, alcohol-associated hepatitis,
and acute-on-chronic liver failure grade 0–2. Poster
presentation to be shared at the 2024 European Association for the
Study of the Liver (EASL) Conference. June 2024.
5 National Organization for Rare
Disorders. Hepatorenal Syndrome. Available at:
https://rarediseases.org/rare-diseases/hepatorenal-syndrome/.
Accessed June 2024.
6 Singh J, Dahiya DS, Kichloo A, Singh G, Khoshbin
K, Shaka H. Hepatorenal Syndrome: A Nationwide Trend Analysis from
2008 to 2018. Annals of Med. 2021;53:1. 2018-2024
doi.org/10/1080/07853890.
7 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