DUBLIN, Sept. 14, 2020 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global
biopharmaceutical company, today announced that the U.S. Food and
Drug Administration (FDA) has issued a Complete Response Letter
(CRL) regarding the company's New Drug Application (NDA) seeking
approval for the investigational agent terlipressin to treat adults
with hepatorenal syndrome type 1 (HRS-1).
The CRL stated that, based on the available data, the agency
cannot approve the terlipressin NDA in its current form and
requires more information to support a positive risk-benefit
profile for terlipressin for patients with HRS-1. HRS-1 is an acute
and life-threatening syndrome involving acute kidney failure in
people with cirrhosis1 for which there is
currently no FDA-approved treatment.2 HRS-1
is estimated to affect between 30,000 and 40,000 Americans
annually,3,4 and often is a
challenge to effectively diagnose in a timely manner due to its
diagnosis of exclusion.5 If left untreated,
HRS-1 has a median survival time of approximately two weeks and
greater than 80 percent mortality within three
months.5,6 U.S. discharge data in a
recently published study indicated an in-hospital mortality rate of
34.2% (n=1,133), while an additional 14.4% (n=475) of patients were
discharged to hospice.7
"While we are disappointed that the FDA issued a complete
response letter for terlipressin, we remain confident in the
strength of the data from our Phase 3 CONFIRM study, which is the
largest clinical trial ever conducted in this rare condition," said
Steven Romano, M.D., Executive
Vice President and Chief Scientific Officer
at Mallinckrodt. "HRS-1 is a complex disease that affects
a critically ill patient population with no approved treatment in
the U.S. at present. We are surprised by and disagree with the
FDA's decision and remain committed to pursuing all available
options as we continue working with the FDA toward approval of
terlipressin in order to help address this difficult and
life-threatening syndrome."
Terlipressin is an investigational agent being evaluated for the
treatment of HRS-1 in the U.S., and its safety and effectiveness
have not yet been established by the FDA.
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-1.8,9 Terlipressin,
together with albumin, is currently the standard of care for HRS-1
in countries where it is
available.10
In 2005, terlipressin was granted Fast Track designation by the
FDA, which provides for expedited review to facilitate development
of drugs intended to treat serious or life-threatening conditions
and fill an unmet medical
need.11 In 2016,
Mallinckrodt and the FDA reached
agreement on the Phase 3 CONFIRM trial protocol design and data
analysis under the agency's special protocol assessment (SPA)
process. A SPA is an advance agreement with the FDA for the
acceptability of the clinical design, endpoints and statistical
data analyses for a Phase 3 trial before the start of the
trial.
On July 15, 2020, the company
announced that the Cardiovascular and Renal Drugs Advisory
Committee of the FDA voted to recommend approval of its
investigational agent terlipressin to treat adults with HRS-1
based, in part, on results from the Phase 3 CONFIRM trial. The
CONFIRM trial was the largest-ever prospective study (n=300)
conducted to assess the safety and efficacy of terlipressin in
patients with HRS-1 for potential use in the U.S. and Canada. Initial results were presented in a
late-breaking session at The Liver Meeting® 2019,
the annual meeting of the American Association for the Study of
Liver Diseases (AASLD).
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,
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 with regard to interactions
with regulators as well as 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-2001369 09/20
References
1 National Organization for Rare
Disorders. Hepatorenal Syndrome. Available
at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/.
Accessed September 12, 2020.
2 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.
3 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
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4 United States Census Bureau: Quick
Facts. Available at:
https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed
September 12, 2020.
5 Gines P, Sola E, Angeli P, et al.
Hepatorenal syndrome. Nature Reviews. 2018;4:23.
6 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.
7 Jamil K, Lodaya K, Tavares R, Huang
X, Hayashida D. The hepatorenal syndrome patient journey: Portrait
of an often-fatal path for those with liver disease. Presented at
Digestive Disease Week® (DDW) Chicago, IL. May 2,
2020 – May 5, 2020.
8 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.
9 Ioannou GN, Doust J, Rockey DC.
Terlipressin for acute esophageal variceal hemorrhage. Cochrane
Database of Systematic Reviews. 2003;1. doi:
10.1002/14651858.CD002147.
10 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.
11 U.S. Food and Drug
Administration (FDA). Fast Track. Available at
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track.
Accessed September 12,
2020.
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