Mallinckrodt Presents New Data on TERLIVAZ® (terlipressin) for Injection at the Society of Critical Care Medicine (SCCM) 2024 Critical Care Congress
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TERLIVAZ's efficacy in improving kidney function in adults with hepatorenal syndrome (HRS) and rapid reduction in kidney function represents a significant advancement in treating this acute and potentially fatal condition. The post hoc analysis of the Phase 3 CONFIRM trial indicates a substantial increase in verified HRS reversal rates when compared to placebo. Considering that HRS affects over 42,000 Americans annually, these findings could herald a considerable impact on patient outcomes and healthcare practices. The data suggests that early recognition and treatment of HRS at lower serum creatinine levels could lead to better patient prognoses.
From a medical research perspective, the implications of these findings are twofold. Firstly, they provide a strong basis for the potential re-evaluation of current treatment protocols for HRS, particularly in the context of alcoholic hepatitis. Secondly, they underline the importance of continuous investment in clinical trials to identify effective treatments for complex conditions like HRS. The critical nature of this condition and its burden on the healthcare system underscore the potential market for effective treatments, which could result in increased demand for TERLIVAZ if its benefits are further validated and recognized by the medical community.
The economic impact of TERLIVAZ extends beyond its clinical benefits. With the increasing rates of HRS hospitalizations, the potential for TERLIVAZ to reduce the duration of hospital stays and the need for renal replacement therapy (RRT) could translate into significant cost savings for the healthcare system. The drug's ability to reverse HRS in a higher percentage of patients compared to placebo may also reduce the overall healthcare burden associated with long-term complications of HRS and liver cirrhosis.
However, the cost-effectiveness of TERLIVAZ will depend on its price point relative to alternative treatments and the cost of managing adverse events associated with its use. The warning regarding serious or fatal respiratory failure is an important consideration for healthcare providers and payers, as it may necessitate additional monitoring and intervention costs. In the long term, the economic value of TERLIVAZ will hinge on its ability to improve patient outcomes and reduce the frequency and severity of costly complications associated with HRS.
The findings from the CONFIRM trial analysis could have a notable impact on Mallinckrodt's market position. As the first and only FDA-approved product for HRS with rapid reduction in kidney function, TERLIVAZ could capture a significant share of the HRS treatment market. The positive results might drive physician adoption and could be leveraged in marketing efforts to differentiate TERLIVAZ from other supportive care options.
However, the pharmaceutical market is sensitive to both clinical efficacy and safety profiles. The Boxed Warning regarding respiratory failure may affect the prescribing behavior of physicians, especially for patients at higher risk of hypoxia. Market uptake will also be influenced by the drug's reimbursement status and the cost-benefit analysis conducted by healthcare institutions. Furthermore, Mallinckrodt's ability to navigate the competitive landscape and secure favorable formulary placements will be crucial for the commercial success of TERLIVAZ.
– Oral presentation of a post hoc analysis of the Phase 3 CONFIRM trial details the therapeutic effect of TERLIVAZ in adult patients with hepatorenal syndrome (HRS) and alcoholic hepatitis (AH)1 –
TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,2 an acute and life-threatening condition requiring hospitalization.3 HRS involving rapid reduction in kidney function2 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4
Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.
The post hoc analysis evaluated the efficacy of TERLIVAZ in a subgroup of patients from the CONFIRM trial with HRS, acute-on-chronic liver failure (ACLF) grade 0–2 and serum creatinine (SCr) <5 mg/dL.1 The incidence of verified HRS reversal – defined as two consecutive SCr values ≤1.5 mg/dL at least two hours apart while on treatment and alive without renal replacement therapy (RRT) for at least 10 days – and HRS reversal – defined as SCr ≤1.5 mg/dL while on treatment – were assessed.1
"We are pleased to share the latest data providing valuable insight into the relationship between TERLIVAZ treatment and rates of verified HRS reversal in adult cirrhosis patients with AH compounded by HRS," said Peter Richardson, MRCP (
A total of 117 patients in the subgroup analysis (N=300) met the criteria for evaluation (TERLIVAZ n=78; placebo n=39).1 The analysis found that the incidence of verified HRS reversal was significantly higher in patients treated with TERLIVAZ vs. placebo (TERLIVAZ:
This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below:
Abstract #1311: Terlipressin Improves Outcomes in Patients with HRS and Alcoholic Hepatitis: The CONFIRM Study1
- Presenter: Jody C. Olson, MD, FACP, Department of Internal Medicine, Mayo Clinic,
Rochester, MN - Presentation Date: Monday, January 22, 2024; 2:30 – 3:30 p.m. MT
- Location: Connections Central – RST 04
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 below90% .
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 function2 is an acute and life-threatening condition that occurs in people with advanced liver disease.3 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.3 HRS involving rapid reduction in kidney function2 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4 If left untreated, HRS with rapid reduction in kidney function2 has a median survival time of less than two weeks and greater than 80 percent mortality within three months.5
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, its potential impact on patients, and the planned presentation regarding the TERLIVAZ trial. 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" 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
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Investor Relations
Daniel J. Speciale
Senior Vice President, Finance and Chief Financial Officer, Specialty Generics
314-654-3638
daniel.speciale@mnk.com
Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@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.
©2024 Mallinckrodt. US-2300993 01/24
References
1 Olson JC, et al. Terlipressin Improves Outcomes in Patients with HRS and Alcoholic Hepatitis: The CONFIRM Study. Oral presentation to be shared at the Society of Critical Care Medicine (SCCM) 2024 Critical Care Congress. January 2024.
2 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023.
3 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed January 2024.
4 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. doi.org/10/1080/07853890.
5 Flamm, S.L., Brown, K., Wadei, H.M., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in
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