volixibat (SAR 548304) / Sanofi, Takeda, Mirum Pharma - LARVOL DELTA

EXPLORING THE ROLE OF ILEAL BILE ACID TRANSPORTER INHIBITORS, LIKE VOLIXIBAT, IN THE REGULATION OF IL-31 AND SERUM BILE ACIDS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: PRELIMINARY RESULTS: FROM THE VANTAGE TRIAL (AASLD 2025) - "Reductions in pruritus after VLX treatment were associated with decreases in both IL-31 and sBA. These findings support the connection between sBA and IL-31 as potential mediators of pruritus in PBC."

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

VOLIXIBAT LEADS TO IMPROVEMENTS IN FATIGUE AND SLEEP FOR ADULTS WITH PRIMARY BILIARY CHOLANGITIS: DATA FROM VANTAGE (AASLD 2025) - "VANTAGE Part 1 results support the hypothesis that efficacious pruritus treatment with VLX may result in improvements in sleep and fatigue in PBC. Improvements in fatigue and sleep will be further evaluated in the ongoing Part 2 period of the VANTAGE study."

Clinical • Cholestasis • CNS Disorders • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • Sleep Disorder

The Role of the Lower Airway Microbiome in Predicting Treatment Response to Immunotherapy in Patients With Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "Phylum-001 was significantlyincreased in non-responders (p = 0.004) while Phylum-002 was enriched inresponders (p = 0.003)...Larger multicentre studies are needed to furtherexplore its potential as a novel biomarker and therapeutic target. ."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

VISTAS: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) (clinicaltrials.gov) - P2 | N=182 | Active, not recruiting | Sponsor: Mirum Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Apr 2027 | Trial primary completion date: Sep 2025 ➔ Jun 2026

Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Pruritus

Intrahepatic Cholestasis of Pregnancy: Diagnosis, Management, and Future Directions-A Review of the Literature. (PubMed, Diagnostics (Basel)) - "Ursodeoxycholic acid (UDCA) remains the primary pharmacologic treatment of intrahepatic cholestasis of pregnancy; however, its effect on perinatal outcomes is debated. Investigational therapies-including Volixibat, FXR agonists, 4-phenylbutyrate, and NorUDCA-are under exploration...Future research should prioritize identifying predictive biomarkers, refining treatment algorithms, and assessing long-term outcomes for both mothers and offspring. Special attention should also be given to the investigation of novel therapeutic targets."

Journal • Review • Cholestasis • Dermatology • Hepatology • Pruritus

VANTAGE: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis (clinicaltrials.gov) - P2 | N=260 | Recruiting | Sponsor: Mirum Pharmaceuticals, Inc. | N=180 ➔ 260 | Trial completion date: Dec 2025 ➔ Jul 2027 | Trial primary completion date: Dec 2025 ➔ Apr 2027

Enrollment change • Trial completion date • Trial primary completion date • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

VOLIXIBAT FOR THE TREATMENT OF CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: AN ADAPTIVE, RANDOMIZED, PLACEBO-CONTROLLED PHASE 2B TRIAL (VANTAGE): INTERIM RESULTS (DDW 2025) - No abstract available

Clinical • P2b data • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

4425: Cholestatic Liver Disease (DDW 2025) - "Description: This session will cover a range of topics, including the risks associated with GLP-1 receptor agonist therapy, the treatment of cholestatic pruritus with Volixibat, and the global burden of chronic liver disease. Attendees will also learn about the role of the ADAM9 gene in cholangiocarcinoma, the impact of obesity on acute liver failure outcomes, and the potential benefits of lipid-lowering therapy in primary sclerosing cholangitis.Learning Objectives:• Describe the association between GLP-1 receptor agonist therapy and the risk of gallbladder and biliary tract disease in individuals with overweight or obesity.• Discuss the role of the ADAM9 gene in mediating prognosis and the immune microenvironment in cholangiocarcinoma."

Biliary Cancer • Cholangiocarcinoma • Cholestasis • Dermatology • Genetic Disorders • Hepatology • Liver Failure • Obesity • Oncology • Pruritus • Solid Tumor • ADAM9

Volixibat Data from Mirum’s VANTAGE PBC Study Showcased at EASL (Businesswire) - P2 | N=180 | VANTAGE (NCT05050136) | Sponsor: Mirum Pharmaceuticals, Inc. | "Data from the interim analysis of VANTAGE were highlighted with new analyses through week 28. Patients were randomized to receive volixibat 20mg BID, 80mg BID, or placebo BID. The primary endpoint of the study was mean change in weekly averaged daily itch score, as measured by the adult ItchRO scale, from baseline to Week 17-Week 28. Volixibat treatment led to rapid (as early as week 1) and sustained reductions in ItchRO with the volixibat combined dose group achieving a statistically significant 3.78-point reduction from Baseline (p<0.0001) and a placebo-adjusted response of 2.51 (p=0.0004). Each volixibat dose achieved statistically significant and similar responses (20mg BID: -2.4 [P=0.0039]; 80mg BID: -2.6 [P=0.0010]). The analysis also provided data across secondary endpoints showing reductions in serum bile acids (sBA) and quality of life (QoL) measures."

P2 data • Primary Biliary Cholangitis

Abstract #OS-059 (Oral): Volixibat for the treatment of cholestatic pruritus in primary biliary cholangitis: an adaptive, randomized, placebo-controlled phase 2B trial (VANTAGE): 28-week interim analysis (Businesswire) - P2 | N=180 | VANTAGE (NCT05050136) | Sponsor: Mirum Pharmaceuticals, Inc. | "New 28-week data were reported from the Phase 2 VANTAGE study evaluating volixibat in patients with cholestatic pruritus related to primary biliary cholangitis (PBC). Thirty-one patients with moderate-to-severe pruritus were randomized (20mg VLX=10, 80mg VLX=10, placebo=11). Data showed that volixibat led to early and significant reductions in PBC-associated cholestatic pruritus and were maintained throughout the duration of the study. Further, 70% of volixibat-treated patients had a ≥50% reduction in serum bile acid levels from baseline. Additionally, patients treated with volixibat experienced improvements in fatigue and sleep. No new safety signals were observed through 28 weeks of treatment. The most common treatment-emergent adverse event was diarrhea which was mild to moderate in severity and transient in nature."

P2 data • Primary Biliary Cholangitis • Pruritus

Volixibat for the treatment of cholestatic pruritus in primary biliary cholangitis: an adaptive, randomized, placebo-controlled phase 2b trial (VANTAGE): 28-week interim results (EASL 2025) - "Volixibat led to early and significant reductions in PBC-associated cholestatic pruritus and fatigue, with no new safety signals observed through 28 weeks of treatment. Given similar results between VLX doses, the 20 mg BID dose was selected for Part 2 of VANTAGE, constituting a new promising therapy to address important symptoms in PBC.."

Clinical • P2b data • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

PILOT STUDY OF VOLIXIBAT CO-ADMINISTERED WITH OCA FOR PRIMARY BILIARY CHOLANGITIS (PBC) TREATMENT: THE VLX-602 TRIAL (AASLD 2024) - "IBAT inhibitors have shown efficacy to treat cholestatic pruritus, including in PBC, but concurrent use of an IBAT inhibitor and obeticholic acid (OCA) is not well studied. These safety pilot study data were consistent with the known safety profile of IBAT inhibitors. The addition of VLX to OCA treatment in PBC led to improvement in itch in some patients, with reversal of the effect upon VLX cessation. The results of this study justify additional investigation of the safety and efficacy of VLX for the treatment of PBC, with or without a background regimen of OCA."

Clinical • Cholestasis • Dermatology • Fatigue • Hepatology • Immunology • Infectious Disease • Primary Biliary Cholangitis • Pruritus • Respiratory Diseases

A Placebo-controlled Study of Volixibat in Subjects With Elevated Serum Bile Acids Associated With Intrahepatic Cholestasis of Pregnancy (OHANA) (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: Mirum Pharmaceuticals, Inc. | Phase classification: P2a/2b ➔ P2

Phase classification • Cholestasis • Hepatology

Positive Interim Analyses of Phase 2b Studies Show Promise for Volixibat in PBC, PSC (HCPLive) - "'The results of the interim analyses are very impressive as they confirm the potential of volixibat in targeting bile acids in PBC and PSC,' Kris Kowdley, MD...said."

Media quote

VISTAS: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) (clinicaltrials.gov) - P2; N=200; Recruiting; Sponsor: Mirum Pharmaceuticals, Inc.; Trial primary completion date: Dec 2022 ➔ Sep 2024

Clinical • Trial primary completion date • Dermatology • Hepatology • Pruritus

VANTAGE: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Mirum Pharmaceuticals, Inc.

Trial completion date • Trial primary completion date • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

VISTAS: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Sclerosing Cholangitis (PSC) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Mirum Pharmaceuticals, Inc. | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial primary completion date • Dermatology • Hepatology • Pruritus

VANTAGE: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Mirum Pharmaceuticals, Inc. | N=260 ➔ 180

Enrollment change • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

EFFICACY, SAFETY AND TOLERABILITY OF VOLIXIBAT IN PATIENTS WITH INTRAHEPATIC CHOLESTASIS OF PREGNANCY: A CASE SERIES OF 4 PATIENTS (AASLD 2023) - P2a/2b | "VLX demonstrated improvements in pruritus and sBA in 4 patients with ICP, signaling proof of concept in this disease. However, studies in pregnancy are inherently difficult to enroll as shown in this trial. These data warrant further research."

Clinical • Cholestasis • Dermatology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Pruritus

Safety, tolerability and efficacy of volixibat, an apical sodium-dependent bile acid transporter inhibitor, in adults with non-alcoholic steatohepatitis: 24-week interim analysis results from a phase 2 study (EASL-ILC 2019) - P2; "Volixibat treatment for 24 weeks did not improve MRI-PDFF, serum ALT or histology in adults with NASH."

Clinical • Late-breaking abstract • P2 data

A Placebo-controlled Study of Volixibat in Subjects With Elevated Serum Bile Acids Associated With Intrahepatic Cholestasis of Pregnancy (OHANA) (clinicaltrials.gov) - P2a/2b | N=4 | Terminated | Sponsor: Mirum Pharmaceuticals, Inc. | N=280 ➔ 4 | Trial completion date: Jan 2024 ➔ Dec 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ Dec 2022; Due to company's assessment of enrollment feasibility.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cholestasis • Hepatology

A Placebo-controlled Study of Volixibat in Subjects With Elevated Serum Bile Acids Associated With Intrahepatic Cholestasis of Pregnancy (OHANA) (clinicaltrials.gov) - P2a/2b | N=280 | Active, not recruiting | Sponsor: Mirum Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cholestasis • Hepatology

"$MIRM discontinue the OHANA study of Volixibat in intrahepatic cholestasis of pregnancy (ICP) due to enrollment feasibility." (@BioStocks)

Cholestasis • Hepatology

VANTAGE: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis (clinicaltrials.gov) - P2; N=260; Recruiting; Sponsor: Mirum Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Dosing ileal bile acid transporter inhibitors in the fasted state minimizes gastrointestinal adverse effects while maintaining pharmacodynamic effect (EASL-ILC 2022) - "IBATi, including maralixibat (MRX; approved for the treatment of cholestatic pruritus in patients with Alagille syndrome [ALGS] ≥1 year of age) and volixibat (VLX), decrease the toxic accumulation of BAs in the liver and mitigate cholestasis. These data demonstrate that GI tolerability is improved when dosing an IBATi in the fasted state, versus dosing at mealtime or immediately after food intake. Animal data show that PD effect is maintained regardless of dosing time relative to mealtime, suggesting that efficacy can be maintained while minimizing GI events."

Adverse events • PK/PD data • Cholestasis • Dermatology • Gastrointestinal Disorder • Hepatology • Pain • Pruritus