DUBLIN, Oct. 29, 2020 /PRNewswire/ -- Mallinckrodt plc, a global biopharmaceutical
company, today announced results from two post-hoc studies of its
investigational agent terlipressin in adults with hepatorenal
syndrome type 1 (HRS-1). HRS-1 is an acute and life-threatening
syndrome involving acute kidney failure in people with
cirrhosis.1 Results were presented at Kidney Week 2020
Reimagined, the annual meeting of the American Society of
Nephrology. The results, based on pooled analyses of three Phase 3
trials including the pivotal CONFIRM study, found that HRS-1
patients treated with terlipressin (N=352) required renal
replacement therapy (RRT) (dialysis) less often and had improved
RRT-free survival up to Day 90 compared to placebo (N=256).
Terlipressin is an investigational agent and its safety and
effectiveness have not yet been established by the U.S. Food and
Drug Administration (FDA).
The results shared in an oral presentation titled "Terlipressin
Improves Renal Replacement Therapy–Free Survival in Hepatorenal
Syndrome Type 1" included a post-hoc analysis to assess the
incidence of RRT among patients from the CONFIRM (NCT 02770716),
REVERSE (NCT 01143246) and OT-0401 (NCT 00089570) Phase 3 trials.
Results from this pooled analysis showed: at Day 30, 26 percent in
the terlipressin group (56/218) needed RRT compared with 42 percent
of those on placebo (70/166); at Day 60, 27 percent of the
terlipressin group (52/193) required RRT versus 45 percent on
placebo (64/143); and at Day 90, 29 percent of surviving patients
in the terlipressin group (52/182) needed RRT compared with 45
percent in the placebo group (60/133).2
The pooled analysis also showed that RRT-free 90-day survival
was higher among patients treated with terlipressin versus placebo
in all three trials. The pooled RRT-free survival rate for patients
treated with terlipressin was 37 percent (130/352) versus 29
percent in the placebo group (73/256) across the three trials
(p=0.03).2 The presentation can be accessed here on the
company's website.
"The findings presented from the post-hoc and pooled analyses
support the positive results of the Phase 3 CONFIRM trial among
HRS-1 patients, showing the potential for terlipressin to help
patients reduce the need for renal replacement therapy and improve
RRT-free survival," said presenting author Juan Carlos Q. Velez, MD, Chair of Nephrology at
Ochsner Health System, New Orleans,
LA. "These findings add to the breadth of existing
knowledge and data of terlipressin, which has been extensively
studied around the world for decades, and are important as HRS-1 is
typically fatal and marked by rapid decline within three months if
left untreated."
Limitations of a pooled analysis such as this include a reliance
on the quality or reporting of the original study results. In
addition, the variability of patient populations, the quality of
the data and the potential for underlying biases are not
addressed.
A second data set was presented in a poster presentation titled,
"Treatment of Hepatorenal Syndrome Type 1 with Terlipressin Reduces
Need for Renal Replacement Therapy After Liver Transplantation,"
including a post-hoc analysis of the CONFIRM study which evaluated
the need for RRT among patients who had liver transplantation at 90
days. The study found that patients treated with terlipressin had a
lower rate of RRT following liver transplantation compared to
patients treated with placebo (19.6 percent (9/46) versus 44.8
percent (13/29); p=0.036). The poster also included a pooled
analysis which assessed survival rates from the three terlipressin
Phase 3 clinical trials for patients following liver
transplantation. The analysis found that at Day 90, 50 percent of
patients treated with terlipressin (46/92) were alive without
receiving RRT compared with 32.2 percent in the placebo group
(19/59; p=0.032).3 The poster can be accessed
here on the company's website.
"Mallinckrodt remains committed to
furthering our understanding of HRS-1 and terlipressin to address
HRS-1, where a patient's condition can deteriorate rapidly and
treatment options are limited," said Steven Romano, M.D., Executive Vice President
and Chief Scientific Officer at Mallinckrodt.
Terlipressin is approved in many countries outside the United States, where it has been a
standard of care for decades in the treatment of patients with
HRS-1.4,5 Terlipressin, together with
albumin, is currently the standard of care for HRS-1 in countries
where it is available.6
HRS-1 has a median survival time of less than two weeks and
greater than 80 percent mortality within three months if left
untreated.7,8 At present, there are no
approved drug therapies for HRS-1 in the U.S.
or Canada.[9] HRS-1 is estimated to affect between 30,000
and 40,000 patients in the U.S. annually.10,11
The studies were funded by Mallinckrodt.
About Terlipressin
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.
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 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,
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 includes forward-looking statements
with regard to terlipressin, 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.
CONTACT
Media Inquiries
Caren
Begun
Green Room Communications
201-396-8551
caren@greenroompr.com
Investor Relations
Daniel J.
Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com
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. ©
2020 Mallinckrodt. US-2000031 10/20
References
1 National Organization for Rare Disorders.
Hepatorenal Syndrome. Available
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Accessed October 16, 2020.
2 Data on file – ref-04410. Mallinckrodt Hospital
Products, Inc.
3 Data on file – ref-04409. Mallinckrodt Hospital
Products, Inc.
4 De Franchis R. Evolving Consensus in Portal
Hypertension Report of the Baveno IV Consensus Workshop on
methodology of diagnosis and therapy in portal hypertension. J
Hepatol. 2005;43:167-176.
5 Ioannou GN, Doust J, Rockey DC. Terlipressin for
acute esophageal variceal hemorrhage. Cochrane Database of
Systematic Reviews. 2003;1. doi: 10.1002/14651858.CD002147.
6 European Association for the Study of the Liver
(EASL). Clinical practice guidelines for the management of patients
with decompensated cirrhosis. J Hepatol.
2018;69(2):406-460.
7 Colle I and Laterre PF. Hepatorenal syndrome: the
clinical impact of vasoactive therapy. Expert Review of
Gastroenterology & Hepatology. (2018) 12:2, 173-188, DOI:
10.1080/17474124.2018.1417034.
8 Gines P, Sola E, Angeli P, et al. Hepatorenal
syndrome. Nature Reviews. (2018) 4:23.
9 Boyer TD, Medicis JJ, Pappas SC, et al. A
randomized, placebo-controlled, double-blind study to confirm the
reversal of hepatorenal syndrome type 1 with terlipressin: the
REVERSE trial design. Open Access Journal of Clinical
Trials 2012:4. https://www.dovepress.com/a-randomized-placebo-controlled-double-blind-study-to-confirm-the-reve-peer-reviewed-article-OAJCT.
10 C Pant, B S Jani, M Desai, A Deshpande,
Prashant Pandya, Ryan Taylor, R Gilroy, M Olyaee. Hepatorenal
syndrome in hospitalized patients with chronic liver disease:
results from the Nationwide Inpatient Sample 2002–2012. Journal
of Investigative Medicine. 2016;64:33–38.
11 United States Census Bureau: Quick Facts.
Available
at: https://www.census.gov/quickfacts/fact/table/US/PST045218.
Accessed October 16, 2020.
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SOURCE Mallinckrodt plc