Mallinckrodt Presents Data on TERLIVAZ® (terlipressin) for Injection in Patients with Hepatorenal Syndrome (HRS) at Kidney Week 2024
Mallinckrodt presented data on TERLIVAZ (terlipressin) for hepatorenal syndrome (HRS) at Kidney Week 2024. The presentation featured a pooled analysis from Phase 3 trials (CONFIRM and REVERSE) examining treatment outcomes in HRS patients. Key findings showed that in patients listed for liver transplant at baseline, TERLIVAZ treatment resulted in 43% HRS-AKI reversal rate compared to 20% in the placebo group. The treatment also reduced the need for renal replacement therapy while maintaining similar liver transplant rates between groups. TERLIVAZ is the first FDA-approved product for improving kidney function in adults with HRS, a condition affecting approximately 42,000 Americans annually.
Mallinckrodt ha presentato dati su TERLIVAZ (terlipressina) per la sindrome epatorenale (HRS) durante la Kidney Week 2024. La presentazione ha evidenziato un'analisi aggregata di studi di Fase 3 (CONFIRM e REVERSE) che esaminano i risultati del trattamento nei pazienti con HRS. I risultati chiave hanno mostrato che nei pazienti in lista per trapianto di fegato all'inizio dello studio, il trattamento con TERLIVAZ ha comportato un tasso di inversione dell'HRS-AKI del 43% rispetto al 20% del gruppo placebo. Il trattamento ha anche ridotto la necessità di terapia di sostituzione renale, mantenendo tassi simili di trapianto di fegato tra i gruppi. TERLIVAZ è il primo prodotto approvato dalla FDA per migliorare la funzione renale negli adulti con HRS, una condizione che colpisce circa 42.000 americani all'anno.
Mallinckrodt presentó datos sobre TERLIVAZ (terlipresina) para el síndrome hepatorrenal (HRS) en la Kidney Week 2024. La presentación incluyó un análisis agrupado de ensayos de Fase 3 (CONFIRM y REVERSE) que examinan los resultados del tratamiento en pacientes con HRS. Los hallazgos clave mostraron que en los pacientes que estaban en lista para trasplante de hígado al inicio del estudio, el tratamiento con TERLIVAZ resultó en una tasa de reversión de HRS-AKI del 43% en comparación con el 20% en el grupo placebo. El tratamiento también redujo la necesidad de terapia de reemplazo renal mientras se mantenían tasas similares de trasplante de hígado entre los grupos. TERLIVAZ es el primer producto aprobado por la FDA para mejorar la función renal en adultos con HRS, una condición que afecta a aproximadamente 42,000 estadounidenses anualmente.
말린크로트는 터리리바즈 (테릴프레신)를 간신증후군(HRS)에 대해 신장 주간 2024에서 발표했습니다. 발표에서는 HRS 환자 치료 결과를 조사한 3상 시험(CONFIRM 및 REVERSE)의 집합 분석이 특징이었습니다. 주요 발견은, 기저선에서 간 이식 대기 중인 환자에서 터리리바즈 치료가 위약 그룹의 20%와 비교하여 43%의 HRS-AKI 역전율을 나타냈다는 것입니다. 치료는 또한 신장 대체 요법의 필요성을 줄이면서 두 그룹 간의 간 이식 비율은 유사하게 유지되었습니다. 터리리바즈는 HRS가 매년 약 42,000명의 미국인에게 영향을 미치는 조건에서 성인의 신장 기능을 향상시키기 위해 FDA에서 승인한 첫 번째 제품입니다.
Mallinckrodt a présenté des données sur TERLIVAZ (térlipressine) pour le syndrome hépato-rénal (HRS) lors de la Kidney Week 2024. La présentation a comporté une analyse groupée des essais de Phase 3 (CONFIRM et REVERSE) examinant les résultats des traitements chez les patients atteints de HRS. Les résultats clés ont montré que chez les patients inscrits sur la liste des transplantations hépatiques au départ, le traitement par TERLIVAZ a abouti à un taux de réversion HRS-AKI de 43 % contre 20 % dans le groupe placebo. Le traitement a également réduit le besoin de thérapie de remplacement rénal tout en maintenant des taux de transplantation hépatique similaires entre les groupes. TERLIVAZ est le premier produit approuvé par la FDA pour améliorer la fonction rénale chez les adultes souffrant de HRS, une condition qui touche environ 42 000 Américains chaque année.
Mallinckrodt stellte Daten zu TERLIVAZ (Terlipressin) für das hepatorenale Syndrom (HRS) bei Kidney Week 2024 vor. Die Präsentation beinhaltete eine Poolanalyse aus Phase-3-Studien (CONFIRM und REVERSE), die die Behandlungsergebnisse bei HRS-Patienten untersuchten. Wichtige Ergebnisse zeigten, dass bei Patienten, die zu Beginn auf die Lebertransplantationsliste gesetzt waren, die Behandlung mit TERLIVAZ eine HRS-AKI-Rückbildungsrate von 43 % im Vergleich zu 20 % in der Placebogruppe ergab. Die Behandlung reduzierte auch die Notwendigkeit einer Nierenersatztherapie, während die Lebertransplantationsraten zwischen den Gruppen ähnlich blieben. TERLIVAZ ist das erste von der FDA zugelassene Produkt zur Verbesserung der Nierenfunktion bei Erwachsenen mit HRS, einer Erkrankung, die jährlich etwa 42.000 Amerikaner betrifft.
- 43% HRS-AKI reversal rate with TERLIVAZ vs 20% with placebo
- Reduced need for renal replacement therapy (28% vs 46% at Day 30)
- First and only FDA-approved treatment for HRS with rapid kidney function reduction
- Small sample sizes in the clinical trials
- efficacy in patients with serum creatinine >5 mg/dL
- Risk of serious or fatal respiratory failure as adverse effect
- Multiple contraindications and safety warnings that may limit patient eligibility
Insights
This pooled analysis from Phase 3 trials of TERLIVAZ shows meaningful clinical outcomes but with mixed implications. The data reveals
However, several factors temper the impact: the small sample size (only 53 patients in treatment group), the serious safety warnings including fatal respiratory failure risk and the eligible patient population (serum creatinine must be <5 mg/dL). The similar liver transplant rates between groups also indicate TERLIVAZ may serve more as a bridge therapy rather than significantly altering disease trajectory.
– Pooled analysis from Phase 3 clinical trials highlights liver transplant rates in adult patients with HRS with rapid reduction in kidney function treated with TERLIVAZ1 –
TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,1 an acute and life-threatening condition requiring hospitalization.2 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually, approximately
Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.
The poster presentation highlights a pooled analysis of data from the CONFIRM and REVERSE Phase 3 placebo-controlled trials of TERLIVAZ.5 The analysis examined the rates of hepatorenal syndrome-acute kidney injury (HRS-AKI) reversal, renal replacement therapy (RRT), and liver transplant (LT) among a subpopulation of patients listed for LT at baseline who met FDA label guidelines for treatment with TERLIVAZ (SCr <5 mg/dL, ACLF grade 0–2, and MELD score <35).5 In this patient subpopulation, treatment with TERLIVAZ increased the rate of HRS-AKI reversal and reduced the need for RRT at all time points assessed.5 The increase in HRS-AKI reversal with TERLIVAZ did not negatively impact the LT rate in patients listed for LT at baseline.5
- The rate of HRS-AKI reversal was
43% in the TERLIVAZ group (n=53) and20% in the placebo group (n=35).5 - The rate of RRT in the TERLIVAZ and placebo groups was
28% and46% by Day 30;32% and54% by Day 60; and36% and54% by Day 90, respectively.5 - The LT rate was similar in the TERLIVAZ and placebo groups at all time points assessed:
53% and51% by Day 30;66% and57% by Day 60; and66% and63% by Day 90, respectively.5
The limitations of this study include, but are not limited to, small sample sizes, variables in methodology, and possible errors and omissions within the data sets.5
"This analysis of data from our Phase 3 trials furthers our understanding of the appropriate patient subpopulations and the potential impact of treatment on liver transplantation rates," said Peter Richardson, MRCP (
This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below:
Poster #PO0102-2: Hepatorenal syndrome-acute kidney injury reversal and liver transplant rates in patients treated with terlipressin5
- Presenter: Justin Belcher
- Session Type: Poster Presentation
- Session Title: AKI: Clinical, Outcomes, and Trials - Management
- Session Date and Time: Saturday, October 26, 2024; 10:00 a.m. – 12:00 p.m. PT
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 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 more than 42,000 Americans annually, approximately
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, and 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: 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" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Mallinckrodt's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, 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
Green Room Communications
908-577-4531
mediainquiries@grcomms.com
Investor Relations
Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com
Mallinckrodt, the "M" brand mark, TERLIVAZ, 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-2400773 10/24
References
1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023.
2 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: https://rarediseases.org/rare-diseases/hepatorenal-syndrome/. Accessed October 2024.
3 United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed October 2024.
4 Singh J., Dahiya D.S., Kichloo A., et al. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021;53:1. 2018-2024 doi.org/10/1080/07853890.
5 Belcher J.M., Regner K.R., Mujtaba M.A., et al. Hepatorenal syndrome-acute kidney injury reversal and liver transplant rates in patients treated with terlipressin. Abstract to be presented at the American Society of Nephrology (ASN) 2024 Annual meeting. October 2024.
6 Flamm, S.L., Brown, K., Wadei, H.M., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in
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SOURCE Mallinckrodt plc
FAQ
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