Kingdom, June 11, 2020
/PRNewswire/ -- Mallinckrodt
plc (NYSE: MNK), a global biopharmaceutical company, today
announced publication of findings from a medical chart study to
assess the real-world use of terlipressin and other vasopressors in
hospitalized patients with hepatorenal syndrome type 1 (HRS-1), an
acute and life-threatening syndrome involving acute kidney failure
in people with cirrhosis.1 The study, funded by
Mallinckrodt, found that terlipressin
was associated with an improvement in kidney function among HRS-1
patients as measured by a reduction in serum creatinine (SCr). The
results of the study were published in the peer-reviewed journal
Alimentary Pharmacology and Therapeutics.
Mallinckrodt is investigating
terlipressin for the treatment of HRS-1 in the U.S. Its safety and
effectiveness have not yet been established by the U.S. Food and
Drug Administration (FDA).
Medical records of 250 adult patients with HRS-1 from 26 centers
in the U.K. were reviewed, 225 of whom were treated with
vasopressor therapy. The majority of patients were treated with
terlipressin (n=203, 90 percent) with a median duration of therapy
of six days, in line with European Association for the Study of the
Liver (EASL) guidelines recommending terlipressin for first-line
use in patients with HRS-1.2 A complete response (SCr
reduction of ≤1.5 mg/dL) was observed in 50 percent of patients
treated with terlipressin and 23 percent of those treated with
other vasopressors. Overall response, as measured by a
complete response or partial response (SCr reduction of at least 20
percent from baseline but SCr >1.5 mg/dL), was demonstrated in
73 percent of patients treated with terlipressin and 59 percent
treated with other vasopressors. In addition, lower SCr at the time
of treatment initiation was associated with higher complete
"While there are limitations to medical chart study, the
findings from this real-world data are encouraging for patients
with HRS-1 who have limited treatment options and are often facing
a poor prognosis," said lead author Kevin Moore, M.D., UCL Institute of Liver and
Digestive Health, Royal Free Hospital, University College
HRS-1 has a median survival time of approximately two weeks and
greater than 80 percent mortality within three months if left
untreated.4,5 At present, there are no approved
drug therapies for HRS-1 in the U.S.
or Canada.6 HRS-1 is estimated to affect
between 30,000 and 40,000 patients in the U.S.
annually.7,8 The company announced in
April the U.S. FDA accepted its New Drug Application for review of
terlipressin to treat HRS-1.
"This retrospective analysis of the use of terlipressin in HRS-1
patients, where it is approved and available, provides important
insight into the real-world treatment patterns and outcomes in this
rare, acute syndrome," said Tunde
Otulana, M.D., Senior Vice President and Chief Medical
Officer at Mallinckrodt. "Mallinckrodt is committed to advancing the science
to benefit patients with this devastating and rapidly progressing
syndrome for which effective treatment options are limited."
About the Study3
The study, titled Real-World Treatment Patterns and Outcomes
Using Terlipressin in 203 Patients with the Hepatorenal
Syndrome, was a medical chart study to assess treatment and
outcomes of terlipressin and other vasopressors in 250 adult
patients with HRS-1 hospitalized in 26 centers in the U.K. between
January 2013 and December
2017. Ninety percent of patients were treated with
terlipressin monotherapy (72 percent in combination with albumin)
with an average treatment duration of six days.
- Terlipressin was associated with improved kidney function: the
overall response rate was 73 percent and the complete response rate
(SCr <1.5 mg/dL) was 50 percent of patients treated with
- Lower SCr at the time of treatment initiation was associated
with higher complete response rates. Mild, moderate and severe
acute kidney injury (AKI) were defined by baseline SCr:
- Mild AKI (SCr <2.25 mg/dL): 79 percent complete
- Moderate AKI (SCr ≥2.25 mg/dL and <3.5 mg/dL): 55 percent
- Severe AKI (SCr ≥3.5 mg/dL): 14 percent complete response.
- The 90-day survival was 86 percent for all patients (93 percent
for overall responders and 66 percent for treatment non-responders,
- Adverse events were attributed to terlipressin in 25 percent of
patients and 41 percent in those treated with other
- Fluid overload/pulmonary edema and multi-organ failure were the
most commonly reported adverse events. Severe AKI was associated
with higher rates of adverse events (41 percent severe AKI versus
25 percent moderate AKI versus 9 percent mild AKI,
- Study Limitations:
- Patients in the retrospective chart study likely represented a
more heterogeneous population than that included in randomized
controlled trials of HRS-1 patients.
- All patients may not have met the full criteria for HRS-1
diagnosis, as diagnosis relies on clinical judgement rather than an
objective diagnostic test.
- Robustness of between treatment difference is uncertain due to
lack of randomization and small number of patients on other
- Changes to the 2015 International Club of Ascites Hepatorenal
Syndrome (ICA-HRS) guidelines, which occurred during the study, may
have altered clinicians' judgement on when to initiate
- The study's sampling strategy may have led to higher survival
and treatment response rates than seen in other settings, leading
to a selection bias towards surviving patients.
Terlipressin is a potent
vasopressin analogue selective for V1 receptors being investigated
for the treatment of HRS-1 in the U.S. and Canada. It is an
investigational product in these countries as the safety and
efficacy have not been established with, nor has approval been
granted by, regulatory authorities in either country. Terlipressin
is approved for use outside the U.S. and Canada.
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,
nephrology, pulmonology and ophthalmology; 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,
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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 with regard to terlipressin and the study described in
this release, 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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©2020 Mallinckrodt. US-2000889. 06/20
1National Organization for Rare Disorders.
Hepatorenal Syndrome. Available
Accessed June 4, 2020.
2European Association for the Study of the Liver.
EASL clinical practice guidelines for the management of patients
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3Moore K, Jamil K, Verleger K, Luo L, Kebede N,
Heisen M, et al. Real–world treatment patterns and outcomes using
terlipressin in 203 patients with the hepatorenal syndrome.
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Taylor, R Gilroy, M Olyaee. Hepatorenal syndrome in
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Nationwide Inpatient Sample 2002–2012. J Investig Med.
8United States Census Bureau: Quick Facts. Available
Accessed June 4, 2020.
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SOURCE Mallinckrodt Pharmaceuticals