Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 24 peer-reviewed journal articles Updated
Hepatology

What Experimental Treatments Are in PSC Clinical Trials?

At a Glance

While there are no FDA-approved treatments for primary sclerosing cholangitis (PSC), active clinical trials are testing experimental drugs. Current research focuses on IBAT inhibitors for severe itching and therapies like oral vancomycin and bile acid modulators to slow disease progression.

In this answer

4 sections

01

The Challenge of PSC Clinical Trials

02

Experimental Drugs for Severe Itching

03

Investigational Drugs Targeting the Disease

04

How to Get Involved in Clinical Trials

There are currently no FDA-approved treatments or cures for primary sclerosing cholangitis (PSC) [1]. Because of this, many motivated patients look toward clinical trials and experimental drugs [2]. While developing therapies for PSC is challenging, research is highly active, focusing on managing debilitating symptoms like itching and targeting the disease process itself through the gut microbiome, bile acids, and inflammation [3][1][4].

The Challenge of PSC Clinical Trials

Developing drugs for PSC is difficult due to its slow, variable progression and the fact that it is a rare disease [2][5]. One of the biggest hurdles is the lack of FDA-approved surrogate endpoints [6]. In clinical trials, a surrogate endpoint is a biomarker (like a blood test) used to quickly measure if a drug is working. In PSC, doctors often monitor alkaline phosphatase (ALP), a liver enzyme [7]. However, there is ongoing debate about whether lowering ALP directly translates to improved long-term outcomes, such as delaying liver failure or the need for a transplant [8][9]. Because of this uncertainty, proving a drug alters the long-term course of PSC takes many years and large patient groups [10].

Before you join a trial, it is helpful to understand the basic stages of research: early phases (Phase 1 and 2) test for safety and basic effectiveness, while later stages (Phase 3) involve hundreds of patients to prove a drug works better than the current standard of care [11]. Trials are closely monitored for safety, but participants should be aware that many studies use a placebo (an inactive “sugar pill”) in a portion of patients to accurately compare the effects of the real drug.

Experimental Drugs for Severe Itching

A major area of research focuses on managing pruritus (severe itching), which is one of the most debilitating symptoms of PSC [4]. Experimental drugs known as IBAT inhibitors (ileal bile acid transporter inhibitors) are currently being tested [4]. These drugs—such as maralixibat, odevixibat, and volixibat—work by blocking the reabsorption of bile acids in the intestines, helping to lower bile acid levels in the blood [12][4][13].

While these medications are highly effective for certain pediatric liver diseases, their impact on adults with PSC requires more research [12]. For example, early trials with maralixibat successfully lowered bile acids in the blood but did not significantly improve severe itching symptoms compared to a placebo [4]. Large-scale trials testing newer drugs like volixibat are ongoing to see if this class of medication can offer meaningful symptom relief [13].

Investigational Drugs Targeting the Disease

Beyond symptom management, several experimental therapies are targeting the underlying disease process:

  • The Gut-Liver Axis: Many researchers believe the gut microbiome plays a role in PSC, especially since many patients also have inflammatory bowel disease (IBD) [14][3]. Clinical trials are exploring fecal microbiota transplantation (FMT) to see if altering gut bacteria can slow disease progression in patients without cirrhosis (advanced, permanent liver scarring) [15]. Oral vancomycin, an antibiotic, is also being studied for its potential to modulate the gut microbiome and lower liver enzymes [16]. However, because it is a potent antibiotic, long-term use carries risks like antibiotic resistance or exacerbating liver injury, which is why rigorous trials are needed before it can become a standard therapy [17][18].
  • Bile Acid Modulators: Drugs like cilofexor work by activating specific receptors in the liver to reduce bile production and inflammation. While earlier studies showed improvements in markers of liver stress, a recent large Phase 3 trial did not show a significant reduction in the progression of fibrosis (early, potentially reversible liver scarring) [19][11].
  • Receptor Agonists for Cholestasis: Medications like elafibranor and seladelpar activate specific cellular pathways to reduce cholestasis (the backup of bile in the liver) [20]. These drugs recently gained accelerated approval for a related liver condition called Primary Biliary Cholangitis (PBC) and are now being researched for their potential to help PSC patients [21][22].

How to Get Involved in Clinical Trials

Enrolling in a clinical trial gives you access to cutting-edge therapies and helps advance the science for everyone living with PSC. Trials typically recruit specific subgroups, such as those with early-stage disease, those with or without cirrhosis, or those with stable IBD [15][19].

  • Search Online: You can actively search for trials currently recruiting patients by visiting ClinicalTrials.gov and searching for “Primary Sclerosing Cholangitis.”
  • Talk to a Specialist: Major hepatology centers and academic research hospitals are the most common sites for PSC trials.
  • Join a Registry: Participating in the PSC Partners Seeking a Cure patient registry is one of the most effective ways to help researchers [23]. The registry collects real-world data on symptoms and disease progression, helping to design better trials and overcome the challenges of researching a rare disease [24][23].

Common questions in this guide

Are there any FDA-approved treatments for primary sclerosing cholangitis?
Currently, there are no FDA-approved medications that cure or stop the progression of primary sclerosing cholangitis. Treatment generally focuses on managing symptoms and complications while researchers actively test experimental drugs in clinical trials.
What experimental drugs are being tested for severe itching in PSC?
Researchers are testing a class of drugs called IBAT inhibitors, including maralixibat, odevixibat, and volixibat. These medications work by blocking the reabsorption of bile acids in the intestines, which may help relieve severe itching.
Can oral vancomycin be used to treat PSC?
Oral vancomycin is an antibiotic currently being studied in clinical trials to see if it can alter the gut microbiome and improve liver enzymes in PSC. However, it is not yet a standard therapy due to the risks of long-term antibiotic use, such as developing antibiotic resistance.
What happens if I get a placebo in a PSC clinical trial?
A placebo is an inactive substance, often referred to as a "sugar pill," used to compare against the experimental drug. In many studies, a portion of participants receive the placebo to help researchers accurately determine if the new drug is truly effective and safe.
How do I find clinical trials for primary sclerosing cholangitis?
You can find actively recruiting clinical trials by searching ClinicalTrials.gov for "Primary Sclerosing Cholangitis." Joining the PSC Partners Seeking a Cure patient registry is also an excellent way to connect with researchers and help advance new treatments.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does your clinic or hospital participate in any active clinical trials for PSC, or can you refer me to a major hepatology center that does?
  2. 2.Based on my recent imaging and blood work, do I have cirrhosis, and how does my disease stage affect my eligibility for clinical trials?
  3. 3.What is my current Alkaline Phosphatase (ALP) level, and how has it trended over the past 12 to 24 months?
  4. 4.If I choose to enroll in a trial, what are the potential risks of stopping my current medications, and what happens if I receive a placebo instead of the experimental drug?
  5. 5.Is oral vancomycin an option we should consider for off-label use while waiting for new treatments, or are the risks of antibiotic resistance too high for my situation?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

Related questions

What is the Best Diet for Primary Sclerosing Cholangitis?CA 19-9 Test: Bile Duct Cancer Screening in PSCWhat is the Difference Between IgG4-SC and PSC?Why is Balloon Dilation Preferred Over Stents for PSC?What Does a FibroScan Score Over 10.5 kPa Mean for PSC?When Should PSC Patients Have Gallbladder Polyps Removed?Is High-Dose URSO Safe for Primary Sclerosing Cholangitis?PSC: Can Recurrent Cholangitis Raise My MELD Score?Will PSC Come Back After a Liver Transplant? ExplainedWhat Is the Difference Between Small & Large Duct PSC?What Are the Third-Line Treatments for Severe PSC Itching?When to Take Cholestyramine with Other PSC MedicationsWhy Do You Need A Colonoscopy For PSC Without Symptoms?

References

References (24)
  1. 1

    Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.

    Fiorucci S, Urbani G, Di Giorgio C, et al.

    Cells 2024; (13(19)) doi:10.3390/cells13191650.

    PMID: 39404413
  2. 2

    Emerging drugs for the treatment of primary sclerosing cholangitis.

    Abbas N, Quraishi MN, Trivedi P

    Current opinion in pharmacology 2022; (62()):23-35 doi:10.1016/j.coph.2021.11.003.

    PMID: 34894541
  3. 3

    Gut-Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis of Primary Sclerosing Cholangitis: An Overview.

    Fousekis FS, Mpakogiannis K, Lianos GD, et al.

    Journal of clinical medicine 2025; (14(21)) doi:10.3390/jcm14217817.

    PMID: 41227212
  4. 4

    Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study.

    Bowlus CL, Eksteen B, Cheung AC, et al.

    Hepatology communications 2023; (7(6)) doi:10.1097/HC9.0000000000000153.

    PMID: 37184523
  5. 5

    Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities.

    Vesterhus M, Karlsen TH

    Journal of gastroenterology 2020; (55(6)):588-614 doi:10.1007/s00535-020-01681-z.

    PMID: 32222826
  6. 6

    Better end points needed in primary sclerosing cholangitis trials.

    Gerussi A, Invernizzi P

    Nature reviews. Gastroenterology & hepatology 2019; (16(3)):143-144 doi:10.1038/s41575-019-0110-5.

    PMID: 30655632
  7. 7

    Longitudinal Comparison of Currently Used Risk Scores for Prognostication of Primary Sclerosing Cholangitis (PSC) in a Hungarian Bicenter PSC Cohort.

    Ven PL, Tornai D, Toth B, et al.

    Diagnostics (Basel, Switzerland) 2025; (15(17)) doi:10.3390/diagnostics15172166.

    PMID: 40941654
  8. 8

    Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, placebo-controlled phase II trial.

    Hirschfield GM, Chazouillères O, Drenth JP, et al.

    Journal of hepatology 2019; (70(3)):483-493 doi:10.1016/j.jhep.2018.10.035.

    PMID: 30414864
  9. 9

    Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis.

    Trivedi PJ, Muir AJ, Levy C, et al.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2021; (19(6)):1248-1257 doi:10.1016/j.cgh.2020.07.032.

    PMID: 32707342
  10. 10

    A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis.

    Kowdley KV, Vuppalanchi R, Levy C, et al.

    Journal of hepatology 2020; (73(1)):94-101 doi:10.1016/j.jhep.2020.02.033.

    PMID: 32165251
  11. 11

    Cilofexor in non-cirrhotic primary sclerosing cholangitis (PRIMIS): a randomised, double-blind, multicentre, placebo-controlled, phase 3 trial.

    Trauner M, Levy C, Tanaka A, et al.

    The lancet. Gastroenterology & hepatology 2026; (11(1)):46-58 doi:10.1016/S2468-1253(25)00208-0.

    PMID: 41173015
  12. 12

    The burden of Alagille syndrome: uncovering the potential of emerging therapeutics - a comprehensive systematic literature review.

    Bufler P, Howard R, Quadrado L, et al.

    Journal of comparative effectiveness research 2025; (14(2)):e240188 doi:10.57264/cer-2024-0188.

    PMID: 39807752
  13. 13

    Intrahepatic Cholestasis of Pregnancy: Diagnosis, Management, and Future Directions-A Review of the Literature.

    Jasak K, Gajzlerska-Majewska W, Jabiry-Zieniewicz Z, et al.

    Diagnostics (Basel, Switzerland) 2025; (15(16)) doi:10.3390/diagnostics15162002.

    PMID: 40870854
  14. 14

    Coexisting inflammatory bowel disease in primary sclerosing cholangitis is associated with higher colorectal cancer and transplant risk.

    Niu C, Zhang J, Bhatta P, et al.

    Journal of internal medicine 2025; (298(6)):626-636 doi:10.1111/joim.70026.

    PMID: 41088845
  15. 15

    FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.

    Al-Shakhshir S, Quraishi MN, Mullish B, et al.

    BMJ open 2025; (15(1)):e095392 doi:10.1136/bmjopen-2024-095392.

    PMID: 39762111
  16. 16

    Microbiome Responses to Vancomycin Treatment in a Child With Primary Sclerosing Cholangitis and Ulcerative Colitis.

    Britto SL, Hoffman KL, Tessier ME, et al.

    ACG case reports journal 2021; (8(5)):e00577 doi:10.14309/crj.0000000000000577.

    PMID: 33997090
  17. 17

    An 'Adaptive Treatment Strategy' for Oral Vancomycin in Patients with the Orphan Disease Primary Sclerosing Cholangitis.

    Shah A, Tabibian J, Buness C, Holtmann GJ

    Digestive diseases and sciences 2024; (69(10)):3608-3613 doi:10.1007/s10620-024-08497-4.

    PMID: 38896361
  18. 18

    Clostridium Scindens Protects Against Vancomycin-Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR-FGF15/19 Signaling.

    Xiao J, Hou Y, Luo X, et al.

    Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2025; (12(5)):e2406445 doi:10.1002/advs.202406445.

    PMID: 39680750
  19. 19

    Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study.

    Levy C, Caldwell S, Mantry P, et al.

    Clinical and translational gastroenterology 2024; (15(8)):e00744 doi:10.14309/ctg.0000000000000744.

    PMID: 38976363
  20. 20

    PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress.

    Hayes CM, Gallucci GM, Boyer JL, et al.

    Hepatology communications 2025; (9(1)) doi:10.1097/HC9.0000000000000612.

    PMID: 39699308
  21. 21

    A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

    Hirschfield GM, Bowlus CL, Mayo MJ, et al.

    The New England journal of medicine 2024; (390(9)):783-794 doi:10.1056/NEJMoa2312100.

    PMID: 38381664
  22. 22

    Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor.

    Jamal F, Elshaer A, Alatout MH, et al.

    Biomedicines 2025; (13(10)) doi:10.3390/biomedicines13102335.

    PMID: 41153623
  23. 23

    Characteristics and Outcomes Reported by Patients With Primary Sclerosing Cholangitis Through an Online Registry.

    Kuo A, Gomel R, Safer R, et al.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2019; (17(7)):1372-1378 doi:10.1016/j.cgh.2018.04.047.

    PMID: 29705262
  24. 24

    Caregiver-reported symptom burden and preferences for therapeutic goals in pediatric primary sclerosing cholangitis.

    Shifman HP, Hatchett J, Pai RA, et al.

    Journal of pediatric gastroenterology and nutrition 2024; (79(4)):835-840 doi:10.1002/jpn3.12287.

    PMID: 38899591

This page provides information on experimental drugs and clinical trials for primary sclerosing cholangitis for educational purposes. It does not replace professional medical advice. Always discuss trial enrollment and treatment options with your hepatologist.

Get notified when new evidence is published on Primary sclerosing cholangitis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.