Terlivaz (terlipressin) / Mallinckrodt - LARVOL DELTA

Terlipressin vs. Somatostatin in Cirrhotic Patients With Acute Gastrointestinal Bleeding and Acute Kidney Injury (clinicaltrials.gov) - P=N/A | N=64 | Not yet recruiting | Sponsor: General Hospital of Shenyang Military Region

New trial • Acute Kidney Injury • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Renal Disease

Impact of CKD on Real-World Outcomes in Patients Treated with Terlipressin for Hepatrorenal Syndrome (HRS)-AKI (KIDNEY WEEK 2025) - "Conclusion In this real-world cohort, more than one-third had pre-existing CKD. Clinical outcomes—including HRS reversal, renal recovery, in-hospital mortality, and home discharge—were not significantly different between CKD and non-CKD patients, suggesting that terlipressin is effective in patients with HRS-AKI, including those with pre-existing CKD, supporting its use across diverse real-world populations."

Clinical • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Hepatology • Hypertension • Immunology • Metabolic Disorders • Nephrology • Portal Hypertension • Renal Disease • Type 2 Diabetes Mellitus

Association of Paracentesis with Hepatorenal Syndrome (HRS) Reversal: Insights from the CONFIRM Trial of Terlipressin (Terli) (KIDNEY WEEK 2025) - P3 | "Other independent factors associated with HRS reversal were SCr (OR 0.39, 95% CI 0.27–0.56, P <.001) and terli tx (OR 3.45, CI 1.80–6.63, P <.001). Conclusion In pts with HRS-AKI, paracentesis was associated with increased odds of HRS reversal and a statistically significant decrease in SCr over 72h."

Acute Kidney Injury • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Renal Disease

Terlipressin for Hepatorenal Syndrome in Patients With Early-Stage Acute-on-Chronic Liver Failure. (PubMed, Liver Int) - P3 | "In patients with HRS-AKI without baseline ACLF grade 3 or SCr ≥ 5 mg/dL, terlipressin improved clinical outcomes and was not associated with an increased risk of respiratory failure."

Clinical • Journal • Acute Kidney Injury • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Failure • Nephrology • Portal Hypertension • Renal Disease • Respiratory Diseases • Transplantation

REVERSAL OF HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY DOES NOT IMPACT LIVER TRANSPLANT RATES (AASLD 2025) - P3 | "In this pooled analysis, terlipressin treatment and achieving HRS reversal were not associated with lower cumulative incidence of liver transplant at 90 days. These findings support the use of terlipressin in appropriate candidates without concern for compromising timely access to liver transplant."

Acute Kidney Injury • Hepatology • Liver Failure • Nephrology • Renal Disease • Transplantation

CORRELATION OF RACE-NEUTRAL GLOMERULAR FILTRATION RATE ASSESSMENT IN LIVER DISEASE (GRAIL 2.0) WITH HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY REVERSAL IN PATIENTS RECEIVING TERLIPRESSIN (AASLD 2025) - P3 | "GRAIL 2.0 identified more pts with HRS reversal despite lower eGFR compared with CKD-EPI 2021. Additionally, GRAIL 2.0 estimated GFR with smaller variance, suggesting greater consistency and potentially greater precision. However, GRAIL 2.0-based assessment did not enhance overall ability to predict terli response."

Clinical • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease

REAL-WORLD TREATMENT PATTERNS AND OUTCOMES AMONG HOSPITALIZED U.S. ADULTS WITH HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY TREATED WITH TERLIPRESSIN (AASLD 2025) - "First-line treatment included terlipressin (22.5%), same-day midodrine and octreotide (26.0%), or norepinephrine (3.2%)... In this real-world HRS cohort treated with terlipressin, most were managed at high-volume centers and had underlying ALD. Although terlipressin was infrequently used first-line, meaningful rates of HRS reversal were observed, particularly in ALD. With nearly half of all patients discharged home and in-hospital mortality under 20%, these findings highlight the potential for terlipressin to improve renal function and overall clinical outcomes–reinforcing the importance of early recognition and treatment."

Clinical • HEOR • Real-world • Real-world evidence • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease

Summary of TERLIVAZ® (terlipressin): the first FDA-approved treatment for HRS in adults with rapid reduction in kidney function (AASLD 2025) - "The Summary of TERLIVAZ® (terlipressin): the first FDA-approved treatment for HRS in adults with rapid reduction in kidney function. TLM theater will highlight the importance of early recognition and current diagnosis and treatment recommendations for hepatorenal syndrome–acute kidney injury (HRS-AKI)."

Clinical • Acute Kidney Injury • Nephrology • Renal Disease

Challenges in the Treatment of Hepatorenal Syndrome-Acute Kidney Injury: A US Chart Review of Treatment Patterns and Survival Outcomes. (PubMed, JGH Open) - "Most patients (85.4%) initiated treatment with midodrine and octreotide for a median of 7 days...Before 2022, hospitalized HRS-AKI patients experienced suboptimal treatment response with off-label treatments and poor survival. There remains an unmet need for safe and effective non-transplant treatments for hospitalized HRS-AKI patients in the United States."

Journal • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Liver Failure • Nephrology • Renal Disease • Transplantation

Early Diagnosis and Timely Terlipressin in Hepatorenal Syndrome Improves Projected Outcomes and Lowers Cost. (PubMed, Clinicoecon Outcomes Res) - "Early intervention is projected to save $11,504 per patient, with total national savings of $460.2 million annually. Based on the modeled projections using data from clinical trial, earlier HRS diagnosis and treatment with terlipressin may improve clinical outcomes, reduce HCRU, and save costs versus current clinical practice."

Journal • Acute Kidney Injury • Critical care • Hepatology • Liver Failure • Nephrology • Renal Disease • Transplantation

Liver Transplantation Rates in Patients with Hepatorenal Syndrome-Acute Kidney Injury Treated with Terlipressin: Effect of Selecting an Appropriate Patient Population (WTC 2025) - P3 | "In the appropriate population, ie, patients with HRS-AKI who met the FDA label criteria, terli treatment led to a statistically significant increase in the rate of HRS reversal vs pbo. Improvement in renal function with terli did not lead to decreased LT rates in the LSP. In general, terli should not be routinely withheld in LT candidates."

Clinical • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Liver Failure • Nephrology • Renal Disease • Transplantation

Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome-Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase III Clinical Studies. (PubMed, Aliment Pharmacol Ther) - P3 | "In a pooled analysis, bradycardia was observed in 6% of terlipressin-treated patients but rarely required a dose interruption or reduction. Arrhythmia SAE incidences were low and similar in both treatment groups. Routine intensive cardiac monitoring for the detection of arrhythmias may not be necessary during terlipressin administration."

Journal • P3 data • Retrospective data • Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Fibrosis • Immunology • Nephrology • Renal Disease

Predictors of response to terlipressin therapy in hepatorenal syndrome: Metabolomic and proteomic analysis from the CONFIRM trial. (PubMed, Hepatol Commun) - "SCr, cystatin C, angiopoietin-2, and beta-2 microglobulin were associated with HRS reversal. Protein and metabolite signals centered on microbiome function and uremic toxins appeared more robust in PT patients, likely selecting a subgroup that may recover without terlipressin. Use of novel biomarkers may enrich for terlipressin response."

Biomarker • Clinical • Journal • Acute Kidney Injury • Chronic Kidney Disease • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Nephrology • Renal Disease • Transplantation • B2M • CST3

IMPROVING THE BENEFIT-TO-RISK PROFILE: EFFICACY OUTCOMES IN PATIENTS WITH HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY WHEN SELECTED ACCORDING TO THE TERLIPRESSIN PRESCRIBING INFORMATION (DDW 2025) - P3 | "The incidence of verified HRS reversal, HRS reversal, and other secondary efficacy endpoints were higher in patients in the LSP vs the non-LSP. Numerically a higher proportion of patients were alive without RRT at Day 30 in the LSP vs the non-LSP, but not at Days 60 and 90, likely because terlipressin does not cure the underlying liver disease. Appropriate patient selection and the use of terlipressin in the LSP improves efficacy outcomes vs the non-LSP."

Clinical • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Liver Failure • Nephrology • Renal Disease

TRANSFORMING HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY TREATMENT: A WIN RATIO ANALYSIS OF TERLIPRESSIN VERSUS PLACEBO (DDW 2025) - P3 | "A total of 598 patients were randomly assigned to receive terlipressin (n=348) or placebo (n=250), resulting in 87,000 matched pairs for treatment comparison. Baseline characteristics were well-balanced between the treatment groups, with a mean age of 54 years in both groups, 39.4% and 36.0% were female in the terlipressin and placebo groups, respectively; mean SCr values were 3.6 mg/dL in both groups, and baseline mean MELD scores were 33.0 and 33.2, in the terlipressin and placebo groups, respectively. The composite mean win ratio was 1.35 (95% CI: 1.15–1.59) in favor of terlipressin over placebo, with terlipressin accounting for 59.7% of total wins."

Clinical • Acute Kidney Injury • Hepatology • Liver Failure • Nephrology • Renal Disease

REAL-WORLD TREATMENT AND OUTCOMES IN HOSPITALIZED PATIENTS WITH HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY AND ALCOHOL-ASSOCIATED LIVER DISEASE (DDW 2025) - "Among a large, comprehensive, hospital-based healthcare dataset in the U.S., two-thirds of adults hospitalized with HRS-AKI and treated with terlipressin had ALD as the underlying liver disease etiology. ALD was more common in men and younger patients. More than half of patients with ALD-related HRS-AKI treated with terlipressin achieved successful HRS reversal, which was associated with lower RRT rates, decreased healthcare resource utilization, and improved patient outcomes."

Clinical • HEOR • Real-world • Real-world evidence • Acute Kidney Injury • Hepatology • Nephrology • Renal Disease

A COMPARATIVE ANALYSIS OF REAL-WORLD HRS-AKI TREATMENT AND OUTCOMES IN THE UK AND US: RAW CLINICAL DATA AND PROPENSITY SCORE-MATCHED EVIDENCE (DDW 2025) - "Background : Terlipressin is the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), but most hospitalized patients in the United States (US) still receive midodrine plus octreotide (MO)... These study results highlight differences in HRS-AKI treatment and outcomes between the UK and US, including the historical standard of care (MO) in the US. In adjusted analyses we found that the real-world use of terlipressin was more effective than MO at improving kidney function."

Clinical data • Real-world • Real-world evidence • Acute Kidney Injury • CNS Disorders • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease

Benefit-to-risk profile in the label-specific population of patients with hepatorenal syndrome-acute kidney injury treated with terlipressin (EASL 2025) - P3 | "Terlipressin improves the rate of HRS reversal vs placebo, especially in the LSP, as compared with the non-LSP. In the terlipressin arm, selection of the LSP vs the non-LSP resulted in approximately a 3.1-times lower incidence of respiratory failure, and a 2.8-times lower incidence of respiratory failure as a cause of death up to 30 days posttreatment. Selection of patients in the LSP leads to an improvement in the benefit-to-risk profile of patients with HRS-AKI treated with terlipressin."

Clinical • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Liver Failure • Nephrology • Renal Disease • Respiratory Diseases

Intermediate-term survival in patients with hepatorenal syndrome-acute kidney injury treated with terlipressin (EASL 2025) - P3 | "Significantly more pts with HRS reversal experienced intermediate-term survival > 90 days without LT, compared with pts without HRS reversal. Lower ACLF score correlated with > 90-day survival without LT in the univariable but not in the multivariate analysis. In the multivariable analysis, HRS reversal was the strongest independent predictor of survival > 90 days without LT, followed by the presence of SIRS, lower MELD score, and alcohol-related etiology of disease."

Clinical • Acute Kidney Injury • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Nephrology • Renal Disease • Systemic Inflammatory Response Syndrome

Mallinckrodt to Present Data on TERLIVAZ (terlipressin) for Injection at the 2025 Digestive Disease Week (DDW) Annual Meeting (PRNewswire) - "Mallinckrodt plc...announced the presentation of four posters and one oral presentation on TERLIVAZ (terlipressin) for injection in patients with hepatorenal syndrome (HRS) with rapid reduction in kidney function, also known as HRS-acute kidney injury (AKI), at Digestive Disease Week (DDW), taking place in San Diego, CA from May 3-6, 2025."

Clinical data • Acute Kidney Injury

Mallinckrodt and Endo to Combine to Create a Global, Scaled, Diversified Pharmaceuticals Leader (PRNewswire) - "Mallinckrodt plc...and Endo, Inc...today announced that they have entered into a definitive agreement to combine in a stock and cash transaction to create a global, scaled, diversified pharmaceuticals leader...Mallinckrodt and Endo plan to combine their generic pharmaceuticals businesses and Endo's sterile injectables business after the close of the transaction and intend to separate that business from the combined company at a later date. Such a separation would be subject to approval by the combined company's Board of Directors and other conditions...The combined company's brands portfolio will comprise leading pharmaceutical brands across a range of therapeutic areas, including XIAFLEX (collagenase clostridium histolyticum), Acthar Gel (repository corticotropin injection), Terlivaz (terlipressin), SUPPRELIN LA (histrelin acetate) and AVEED (testosterone undecanoate)."

M&A • Ankylosing Spondylitis • Diabetic Nephropathy • Fibrosis • Immunology • Lupus • Multiple Sclerosis • Ocular Inflammation • Prostate Cancer • Psoriatic Arthritis • Renal Disease • Rheumatoid Arthritis • Sarcoidosis • Systemic Lupus Erythematosus • Uterine Leiomyoma

Mallinckrodt plc Reports Fourth Quarter and Fiscal Year 2024 Financial Results and Provides 2025 Guidance (PRNewswire) - "Acthar Gel net sales were $138.8 million in the fourth quarter, an increase of 33.0% versus the prior year period, and $485.7 million for the full year, an increase of 14.2%...Terlivaz net sales were $6.1 million in the fourth quarter, up from $5.6 million in the same period last year, and $24.7 million for the full year, up from $15.6 million...INOmax (nitric oxide) net sales were $60.8 million in the fourth quarter, down 14.0% compared to the prior year period, and full-year net sales were $261.4 million, down 13.8%, primarily due to competitive pressures in the U.S."

Sales • Ankylosing Spondylitis • Diabetic Nephropathy • Lupus • Multiple Sclerosis • Myositis • Ocular Inflammation • Psoriatic Arthritis • Pulmonary Arterial Hypertension • Renal Disease • Rheumatoid Arthritis • Sarcoidosis • Steven-Johnson Syndrome • Systemic Lupus Erythematosus

The relationship between mean arterial pressure and terlipressin in hepatorenal syndrome-acute kidney injury reversal: a post hoc analysis. (PubMed, Hepatology) - "These data highlight that terlipressin leads to an early, sustained increase in MAP, which is a key pharmacodynamic target for HRS-AKI reversal."

Journal • Retrospective data • Acute Kidney Injury • Nephrology • Renal Disease

Defining Renal Recovery in Patients With Hepatorenal Syndrome-Acute Kidney Injury: Experience From North American Studies. (PubMed, JGH Open) - "Additionally, the overall survival and RRT-free survival in the group that achieved > 30% improvement in SCr without HRS reversal were comparable to the overall group that achieved HRS reversal. A total of > 30% improvement in SCr levels even without HRS reversal may serve as a clinically meaningful endpoint to define renal recovery in patients with HRS-AKI."

Journal • Acute Kidney Injury • Nephrology • Renal Disease • Transplantation

Retreatment Following Initial Treatment With Terlipressin Improved Clinical Outcomes Among Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Pooled Post Hoc Analysis (ACG 2024) - "There was a significant improvement in HRS reversal and durable HRS reversal with initial terlipressin treatment versus placebo (HRS reversal: 33.2% [117/352] vs 16.4% [42/256], P < .001; durable HRS reversal, 30.1% [106/352] vs 15.2% [39/256], P < .001). Moreover, HRS reversal was durable among most patients with initial reversal (terlipressin, 90.6% [106/117]; placebo, 92.9% [39/42]). Ten patients eligible for retreatment with terlipressin were retreated, with a median time to retreatment of 21 days (range: 12–75 days)."

Clinical • Clinical data • Retrospective data • Acute Kidney Injury • Nephrology • Renal Disease