Terlivaz (terlipressin) / Mallinckrodt - LARVOL DELTA

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

Trends in the Early Adoption of Terlipressin Among Hospitalized Adults with Hepatorenal Syndrome in the U.S.: A Real-World Analysis (ACG 2024) - "On average (SD), terlipressin was initiated on day 6 (6.7) of hospitalization, and only 20.8% (n= 26) received terlipressin as 1 st line treatment; 78.4% were treated first with midodrine or octreotide (53.6% received both), and 11.2% with norepinephrine (not mutually exclusive)... A total of 125 patients were included. Mean age was 55.4y ± 12.5, 67.2% were male, 64.8% were White (non-Hispanic), 17.6% were Hispanic, and 8.8% were Black/African American (non-Hispanic). Nearly all patients had an index hospitalization classified as emergent/urgent (97.6%), 84.8% sought care from teaching hospitals, and 64.8% were treated at large hospitals with 500+ beds."

Clinical • Real-world • Real-world evidence • Acute Kidney Injury • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Renal Disease

Hepatorenal Syndrome-AKI Reversal and Liver Transplant Rates in Patients Treated with Terlipressin (KIDNEY WEEK 2024) - "Terli increased the rate of HRS-AKI reversal and reduced the need for RRT vs pbo. Importantly, the increase in HRS-AKI reversal in the terli group (vs pbo) did not negatively impact the LT rate in pts listed for LT at baseline in the population meeting the FDA criteria for terli treatment."

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

Terlipressin use in hepatorenal syndrome-acute kidney injury in cirrhosis. (PubMed, Intensive Care Med) - No abstract available

Journal • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease

TERLIVAZ® (terlipressin): the First FDA-approved Treatment for HRS in Adults with Rapid Reduction in Kidney Function (AASLD 2024) - "Supported by Mallinckrodt Pharmaceuticals. Consider treatment with the first and only FDA-approved drug for HRS in adults with rapid reduction in kidney function: TERLIVAZ® (terlipressin) Terlipressin is recommended by AASLD Guidance and ACG guidelines Demonstrated a significantly higher rate of verified HRS reversal, defined as improvement in renal function, avoidance of dialysis, and short-term survival Treatment earlier in disease progression was associated with a higher rate of HRS reversal and lower rate of respiratory failure Terlipressin can be used to treat patients outside of the ICU on the regular medical floor The most commonly observed adverse reactions in patients treated with terlipressin were abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea."

Clinical • Pain • Pulmonary Disease • Respiratory Diseases

ROLE OF HIGH VERSUS STANDARD DOSE OF TERLIPRESSIN IN REVERSING HRS-AKI: POOLED ANALYSIS FROM PHASE 3 CLINICAL TRIALS (AASLD 2024) - "Terli can be dose-escalated to 2 mg Q6H in patients who do not achieve adequate improvement in SCr by Day 4. Among patients who had a dose escalation, the HRS reversal rate was 40%. While the overall SAE safety profiles were comparable between the std and high dose of terli, certain SAEs were slightly higher (2–4%) in the high-dose group."

P3 data • Retrospective data • Acute Kidney Injury • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease • Respiratory Diseases

THE IMPACT OF TERLIPRESSIN TREATMENT ON LIVER TRANSPLANTATION RATES IN PATIENTS WITH HEPATORENAL SYNDROME-ACUTE KIDNEY INJURY (HRS-AKI) IN THE CONTEXT OF THE CHANGING MELD SCORE DEFINITIONS (AASLD 2024) - P3 | "Improvement in MELD due to terli treatment did not lead to a decrease in transplantation rate, despite a decrease in all 3 MELD score variants for terli vs pbo in the mitigated population. The rates of LT and SLKT in this population were similar in both treatment arms."

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

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 (AASLD 2024) - "Among those who responded with HRS reversal by EOT, most patients needed at least 12 doses of treatment with terli. These results indicate that terli should be used for an adequate amount of time (ie, 4 days) at the initial standard dose before a clinical decision for discontinuation is made."

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

THE EFFECT OF OBESITY ON THE CLINICAL RESPONSE TO TERLIPRESSIN IN PATIENTS WITH HEPATORENAL SYNDROME: RETROSPECTIVE ASSESSMENT FROM A POOLED PATIENT COHORT (AASLD 2024) - "Pts with HRS-AKI and obesity (cBMI >30 kg/m2) who were treated with terli achieved significantly more HRS reversal vs pbo, similar to pts with a cBMI ≥25–≤30 kg/m2, and cBMI <25 kg/m2. Thus, demonstrating that terli treatment provides clinical benefit to pts with HRS-AKI, regardless of BMI subgroup."

Retrospective data • Acute Kidney Injury • Fibrosis • Gastroenterology • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Obesity • Renal Disease

PROTEOMIC AND METABOLOMIC ANALYSIS FROM THE CONFIRM TRIAL SHOWS BIOMARKERS THAT PREDICT HRS REVERSAL WITHOUT VASOCONSTRICTOR THERAPY (AASLD 2024) - "Cystatin C, angiopoietin-2, and beta-2 microglobulin, were associated with HRS response. Protein and metabolites centered on microbiome function and uremic toxins appeared more robust in placebo-treated patients. The latter suggests that these may be biomarkers to determine which patients may reverse HRS without vasoconstrictor therapy."

Biomarker • Omic analysis • Fibrosis • Hepatology • Immunology • Nephrology • Renal Disease • B2M • CST3 • FABP1 • IL18 • KIM1 • SPP1

Early diagnosis and treatment with Terlipressin for adults with hepatorenal syndrome improves clinical outcomes and reduces healthcare resource utilization (EASL-ILC 2024) - "A recent analysis of 3 North American clinical trials showed that patients with lower serum creatinine (SCr) levels at diagnosis derived greater benefit from terlipressin (TERLIVAZ®), emphasizing the importance of early identification and treatment of HRS... Earlier HRS diagnosis and treatment with terlipressin shows improved clinical outcomes including transplant-free survival and reduced healthcare resource utilization compared to the current clinical practice."

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