Mallinckrodt to Present Data on TERLIVAZ® (terlipressin) for Injection in Adult Patients with Hepatorenal Syndrome (HRS) at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting

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Nov 03, 2022, 06:53 ET

– Seven scientific abstracts spanning clinical and health economic outcomes research will be presented at the AASLD Liver Meeting, showcasing the breadth of Mallinckrodt's commitment to HRS patients with rapid reduction in kidney function¹ –

DUBLIN, Nov. 3, 2022 /PRNewswire/ -- Mallinckrodt plc (NYSE American: MNK), a global specialty pharmaceutical company, today announced that seven scientific abstracts on clinical and health economic outcomes research on treatment with TERLIVAZ^® (terlipressin) for adult patients with hepatorenal syndrome (HRS) involving rapid reduction in kidney function,¹ an acute and life-threatening condition requiring hospitalization² will be presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting in Washington, DC, from November 4-8. TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome (HRS).¹

Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.

The findings from a subgroup analysis of the CONFIRM trial, selected as AASLD's "Best of Liver Meeting" abstract, presented by Dr. Ethan Weinberg, University of Pennsylvania, Philadelphia, PA, examined long-term clinical outcomes of terlipressin-treated patients with HRS type 1 (HRS-1) who received a liver transplant compared with those who received placebo.³ Furthermore, an interim analysis of the INFUSE study examining the investigational use of continuous terlipressin infusion for patients with HRS acute kidney injury (AKI-HRS) was selected as an "AASLD Presidential Poster of Distinction," to be presented by Dr. K. Rajender Reddy, University of Pennsylvania Perelman School of Medicine, Division of Gastroenterology and Hepatology, Philadelphia, PA.⁴ TERLIVAZ is only approved for intravenous (IV) bolus dosing.¹

Additional information on Dr. Weinberg's and Dr. Reddy's studies and the full list of Mallinckrodt's presentations can be found below.

"We look forward to sharing our breadth of data across clinical research and treatment paradigms with terlipressin as well as health economic outcomes assessments uncovering the associated economic and healthcare resource burden for healthcare systems and patients with HRS with rapid reduction in kidney function.¹ These findings not only provide valuable insight into the association between patient characteristics and long-term treatment outcomes, but also help to highlight the inherent clinical and economic burden HRS patients and providers face in the U.S., and the need for additional options," said Khurram Jamil, Vice President, Hepatology, Clinical Development & Critical Care. "In light of the recent FDA approval of TERLIVAZ, and exemplified through our ongoing research efforts, Mallinckrodt's commitment to improving treatment outcomes in HRS remains strong, and we are hopeful that we are one step closer to addressing the unmet needs of critically ill patient populations."

These studies are sponsored by Mallinckrodt Pharmaceuticals and include:

Abstract 164: Pretransplant Terlipressin Treatment for Hepatorenal Syndrome Decreases the Need for Renal Replacement Therapy both Pre- and Posttransplant: A 12-month Follow-up Analysis of the CONFIRM Trial³

Presenter: Ethan Weinberg, MD, MS
Presentation Date: November 7, 2022; 9:15AM ET
Location: Room 202, Walter E. Washington Convention Center
*SELECTED AS "BEST OF LIVER MEETING"

Abstract 163: Rebound in Serum Creatinine Levels After Terlipressin-based Treatment of Patients with Acute Kidney Injury-Hepatorenal Syndrome (HRS-AKI) is Uncommon Over the Short Term in Patients with a Complete Response: Results from the CONFIRM Study⁵

Presenter: Ethan Weinberg, MD, MS
Presentation Date: November 7, 2022; 10:15 AM ET
Location: Room 202, Walter E. Washington Convention Center

Abstract 3703: Partial Response to Terlipressin Therapy, as per International Club of Ascites (ICA) Criteria, is Associated with a Lower End-of-treatment Acute-on-chronic Liver Failure Grade and Fewer Organ Failures in Patients with Hepatorenal Syndrome Type 1 (HRS)⁶

Presenter: Florence Wong, MD
Presentation Date: November 6, 2022; 1:00 PM ET
Location: Poster Hall, Hall E, Walter E. Washington Convention Center

Abstract 3656: Safety and Efficacy of Continuous Infusion Terlipressin in AKI-HRS: The INFUSE Study⁴

Presenter: K. Rajender Reddy, MD, FAASLD
Presentation Date: November 6, 2022; 1:00 PM ET
Location: Poster Hall E, Walter E. Washington Convention Center
* AASLD Presidential Poster of Distinction

Abstract 3714: Cost Per Response with Terlipressin Versus Standard of Care in Hepatorenal Syndrome Patients⁷

Presenter: John A. Carter, MD
Presentation Date: November 6, 2022; 1:00 PM ET
Location: Poster Hall, Hall E, Walter E. Washington Convention Center

Abstract 3719: Real-world Patient Characteristics, Treatment, and Outcomes for Hepatorenal Syndrome: Evidence from the U.S. and UK Medical Chart Studies⁸

Presenter: Andrew S. Allegretti, MD
Presentation Date: November 6, 2022; 1:00 PM ET
Location: Poster Hall, Hall E, Walter E. Washington Convention Center

Abstract 3699: Retrospective Analysis of Treatment Response in Patients with Hepatorenal Syndrome/Acute Kidney Injury (HRS-AKI): Real-world Evidence from 2016-2020⁹

Presenter: Xingyue Huang, PhD
Presentation Date: November 6, 2022; 1:00 PM ET
Location: Poster Hall, Hall E, Walter E. Washington Convention Center

Find more information on the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting Website.

Terlipressin is one of the most studied pharmacological agents in HRS with more than 70 published manuscripts and presented abstracts on clinical data to date.¹⁰ It has been approved outside the U.S. for more than 30 years and is available on five continents for its indications in the countries where it is approved.^11,12

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 between 30,000 and 40,000 Americans annually.^13,14 If left untreated, HRS with rapid reduction in kidney function¹ has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.¹⁵

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 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; cultured skin substitutes 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 TERLIVAZ, 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
Heather Guzzi
Senior Vice President, Green Room Communications
973-524-4112
[email protected]

Investor Relations
Daniel J. Speciale
Global Corporate Controller & Chief Investor Relations Officer
314-654-3638
[email protected]

Derek Belz
Vice President, Investor Relations
314-654-3950
[email protected]

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.

References

¹ TERLIVAZ^® (terlipressin) for injection [prescribing information]. Mallinckrodt Hospital Products Inc.
² National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed October 20, 2022.
³ Weinberg E. Pretransplant Terlipressin Treatment for Hepatorenal Syndrome Decreases the Need for Renal Replacement Therapy both Pre- and Posttransplant: A 12-month Follow-up Analysis of the CONFIRM Trial. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁴ Reddy KR. Safety and Efficacy of Continuous Infusion Terlipressin in AKI-HRS: The INFUSE Study. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁵ Weinberg E. Rebound in Serum Creatinine Levels After Terlipressin-based Treatment of Patients with Acute Kidney Injury-Hepatorenal Syndrome (HRS-AKI) is Uncommon Over the Short Term in Patients with a Complete Response: Results from the CONFIRM Study. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁶Wong F. Partial Response to Terlipressin Therapy, as per International Club of Ascites (ICA) Criteria, is Associated with a Lower End-of-treatment Acute-on-chronic Liver Failure Grade and Fewer Organ Failures in Patients with Hepatorenal Syndrome Type 1 (HRS). To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁷ Carter JA. Cost Per Response with Terlipressin Versus Standard of Care in Hepatorenal Syndrome Patients. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁸ Allegretti AS. Real-world Patient Characteristics, Treatment, and Outcomes for Hepatorenal Syndrome: Evidence from the U.S. and UK Medical Chart Studies. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
⁹ Huang X. Retrospective Analysis of Treatment Response in Patients with Hepatorenal Syndrome/Acute Kidney Injury (HRS-AKI): Real-world Evidence from 2016-2020. To be Presented at the American Association for the Study of Liver Diseases (AASLD) 2022 Liver Meeting. November 2022.
¹⁰ Data on File – Ref-05488. Mallinckrodt Pharmaceuticals.
¹¹ Data on File – Ref-05482. Mallinckrodt Pharmaceuticals.
¹² FDA Cardiovascular and Renal Drugs Advisory Committee. Mallinckrodt Pharmaceuticals Terlipressin Advisory Committee Briefing Document NDA #022231. July 2020.
¹³ C Pant, B S Jani, M Desai, A Deshpande, Prashant Pandya, Ryan Taylor, R Gilroy, M OIyaee. Hepatorenal syndrome in hospitalized patients with chronic liver disease: results from the Nationwide Inpatient Sample 2002-2012. J of Investig Med. 2016; 64:33-38.
¹⁴ United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed October 20, 2022.
¹⁵ Flamm SL, Brown K, Wadei HM., 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.