Mallinckrodt Presents Data on TERLIVAZ® (terlipressin) for Injection in Patients with Hepatorenal Syndrome (HRS) at the 2024 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
Mallinckrodt presented data on TERLIVAZ (terlipressin) for hepatorenal syndrome (HRS) at the 2024 AASLD Annual Meeting. The research analyzed pooled data from three Phase 3 studies, evaluating HRS reversal after 12 doses. Results showed 33.6% reversal rate in the TERLIVAZ group versus 16.8% in placebo. Notably, 94.9% of patients achieving HRS reversal required more than 12 doses. TERLIVAZ is the first FDA-approved treatment 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 hepatorenale (HRS) durante la Riunione Annuale AASLD del 2024. La ricerca ha analizzato dati aggregati provenienti da tre studi di Fase 3, valutando la reversibilità dell'HRS dopo 12 dosi. I risultati hanno mostrato un tasso di reversibilità del 33,6% nel gruppo TERLIVAZ rispetto al 16,8% nel gruppo placebo. Nota importante, il 94,9% dei pazienti che hanno raggiunto la reversibilità dell'HRS ha richiesto più di 12 dosi. TERLIVAZ è il primo trattamento approvato dalla FDA per migliorare la funzione renale negli adulti con HRS, una condizione che colpisce circa 42.000 americani ogni anno.
Mallinckrodt presentó datos sobre TERLIVAZ (terlipresina) para el síndrome hepatorrenal (HRS) en la Reunión Anual AASLD 2024. La investigación analizó datos agrupados de tres estudios de Fase 3, evaluando la reversión de HRS después de 12 dosis. Los resultados mostraron una tasa de reversión del 33,6% en el grupo TERLIVAZ frente al 16,8% en el placebo. Notablemente, el 94,9% de los pacientes que lograron la reversión de HRS necesitaron más de 12 dosis. TERLIVAZ es el primer tratamiento aprobado por la FDA para mejorar la función renal en adultos con HRS, una condición que afecta a aproximadamente 42,000 estadounidenses anualmente.
몰린크롯은 2024 AASLD 연례 회의에서 간신 증후군(HRS)을 위한 TERLIVAZ (테르 리프레신)에 대한 데이터를 발표하였습니다. 이 연구는 3개의 3상 연구에서 집계된 데이터를 분석하였으며, 12회의 투여 후 HRS 개선을 평가하였습니다. 결과는 TERLIVAZ 그룹에서 33.6%의 개선률을 보였고, 위약 그룹에서는 16.8%였습니다. notably, HRS 개선을 이룬 환자 중 94.9%는 12회 이상의 투여가 필요했습니다. TERLIVAZ는 HRS가 있는 성인의 신장 기능 개선을 위한 최초의 FDA 승인 치료제이며, 이 상태는 매년 약 42,000명의 미국인에게 영향을 미칩니다.
Mallinckrodt a présenté des données sur TERLIVAZ (térelipressine) pour le syndrome hépatoténal (HRS) lors de la réunion annuelle AASLD 2024. La recherche a analysé des données regroupées provenant de trois études de phase 3, évaluant l'inversion de l'HRS après 12 doses. Les résultats ont montré un taux d'inversion de 33,6% dans le groupe TERLIVAZ contre 16,8% dans le placebo. Notamment, 94,9% des patients ayant atteint l'inversion de l'HRS ont nécessité plus de 12 doses. TERLIVAZ est le premier traitement approuvé par la FDA pour améliorer la fonction rénale chez les adultes atteints d'HRS, une condition touchant environ 42 000 Américains chaque année.
Mallinckrodt präsentierte Daten zu TERLIVAZ (Terlipressin) für das hepatorenale Syndrom (HRS) auf dem 2024 AASLD Jahresmeeting. Die Forschung analysierte gepoolte Daten aus drei Phase-3-Studien zur Bewertung der HRS-Reversibilität nach 12 Dosen. Die Ergebnisse zeigten eine Reversibilitätsrate von 33,6% in der TERLIVAZ Gruppe im Vergleich zu 16,8% in der Placebo-Gruppe. Bemerkenswert ist, dass 94,9% der Patienten, die eine HRS-Reversibilität erreichten, mehr als 12 Dosen benötigten. TERLIVAZ ist die erste von der FDA zugelassene Behandlung zur Verbesserung der Nierenfunktion bei Erwachsenen mit HRS, einer Erkrankung, die jährlich etwa 42.000 Amerikaner betrifft.
- TERLIVAZ showed significantly higher HRS reversal rate (33.6%) compared to placebo (16.8%)
- First and only FDA-approved product for HRS with rapid reduction in kidney function
- Addresses an unmet medical need affecting 42,000 Americans annually
- 94.9% of patients required extended treatment beyond 12 doses for effectiveness
- Risk of serious or fatal respiratory failure, particularly in patients with volume overload
- Potential adverse reactions may make patients ineligible for liver transplantation
Insights
This poster presentation at AASLD on TERLIVAZ offers clinically relevant but financially non-impactful data. The key findings show that 33.6% of TERLIVAZ patients achieved HRS reversal compared to 16.8% in the placebo group, with 94.9% of successful cases requiring more than 12 doses. While this supports the drug's efficacy and optimal treatment duration, it represents routine clinical research rather than market-moving news.
The target market is notably small, affecting only 42,000 Americans annually (
– Poster evaluates potential impact of waiting until Day 4 (and after 12 doses of TERLIVAZ) before assessing outcomes in adult patients with HRS with rapid reduction in kidney function1 –
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 includes a pooled patient cohort analysis from the CONFIRM, REVERSE, and OT-0401 Phase 3 studies of TERLIVAZ.5 The research evaluated HRS reversal among patients on Day 4 after 12 doses of TERLIVAZ.5 TERLIVAZ treatment is recommended at a dose of 1 mg every six hours for up to 14 days, which can be escalated on Day 4 to 2 mg every six hours if the patient's serum creatinine (SCr) has decreased from baseline but by less than
- The rate of HRS reversal by the end of treatment was
33.6% (117/348) in the TERLIVAZ group and16.8% (42/250) in the placebo group.5 - Most patients who achieved HRS reversal with TERLIVAZ received >12 doses (
94.9% , 111/117), and5.1% (6/117) received ≤12 doses before discontinuation.5 - There appeared to be significantly more patients who achieved HRS reversal in the TERLIVAZ group who received >12 doses, but not among those who received ≤12 doses; however, based on the design of the analysis, statistical methodology did not control for confounding variables, thus the p-values are nominal.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
"We are pleased to share research which evaluated HRS reversal among patients after 12 doses or on Day 4 of treatment," said Peter Richardson, MRCP (
This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below:
Poster #4094: Patience is a Virtue: Evidence for Waiting Until Day 4 and After 12 Doses of Terlipressin Before Evaluating Treatment Response in Patients with HRS-AKI5
- Presenter: Manhal J. Izzy
- Session Type: Poster Presentation
- Session Title: Portal Hypertension and Other Complications of Cirrhosis
- Session Date and Time: Monday, November 18, 2024; 8:00 a.m. – 5:00 p.m. PST
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 disease2 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-2400840 11/24
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 November 2024.
3 United States Census Bureau: Quick Facts. Available at: https://www.census.gov/quickfacts/fact/table/US/PST045218. Accessed November 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 Izzy, M.J., Gonzalez, S.A., Jalal, P.K., and Cardoza, S. Patience is a Virtue: Evidence for Waiting Until Day 4 and After 12 Doses of Terlipressin Before Evaluating Treatment Response in Patients with HRS-AKI. Abstract to be presented in a poster presentation at the American Association for the Study of Liver Diseases – The Liver Week Meeting. November 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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