Drug discovery
38
drugs
With orphan designations
Overview
Primary Sclerosing Cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive inflammation, fibrosis, and stricturing of intra- and extrahepatic bile ducts. It is strongly associated with inflammatory bowel disease (IBD) in 70–80% of cases [1][6][12]. Clinical manifestations include fatigue, pruritus, jaundice, and recurrent cholangitis, with late-stage complications such as cirrhosis, portal hypertension, and hepatobiliary cancers (e.g., cholangiocarcinoma in 10–15% of patients) [1][12][20]. Diagnosis relies on cholangiography (MRCP/ERCP) and exclusion of secondary causes [1][6]. Liver transplantation is the only curative option for advanced disease, though recurrence occurs in 25–30% of cases [12][16].
Burden
Survival: Median transplant-free survival 21 years; 50% mortality at 21 years post-diagnosis [9][12].
Cancer risk: 10–15% lifetime risk of cholangiocarcinoma; 10-fold increased risk of colorectal cancer in IBD patients [12][20].
Quality of life: 48% loss of quality-adjusted life years (QALYs) >25 years post-diagnosis, 25% work productivity loss [9].
Healthcare utilization: Annual costs ~€12,169/patient, with 12.4 hospital contact days/year [9][10].
Therapies
Symptom management: Pruritus treated with cholestyramine, rifampicin, or opioid antagonists; antibiotics for recurrent cholangitis [3][8][13].
Endoscopic intervention: Balloon dilation/stenting for dominant strictures [3][13].
Liver transplantation: Indicated for decompensated cirrhosis or cholangiocarcinoma; 10-year survival post-transplant >80% [4][9][16].
No disease-modifying therapies exist, though high-dose ursodeoxycholic acid (13–15 mg/kg/day) is commonly used [3][5].
Categories: rare hepatic diseases, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
volixibat | small molecules | FDA | 2026-07-21 | — | Mirum Pharmaceuticals, Inc. |
Leuconostoc citreum, strain G511, Live | other | EMA | 2025-11-21 | — | Harvest Integrated Research Organization Ireland Limited |
Elafibranor | small molecules | EMA | 2025-07-18 | — | Ipsen Pharma |
elafibranor | small molecules | FDA | 2025-07-16 | — | IPSEN Bioscience Inc. |
Beta-lapachone | small molecules | EMA | 2025-06-20 | — | Hungarotrial Zrt. |
Volixibat potassium | small molecules | EMA | 2025-02-26 | — | Mirum Pharmaceuticals International B.V. |
small molecule inhibitor of hyaluronan synthesis | small molecules | FDA | 2024-04-09 | — | Halo Biosciences, Inc. |
Aldafermin | proteins | FDA | 2023-12-21 | — | NGM Biopharmaceuticals Inc. |
Live biotherapeutic product consisting of a single bacterial strain (Leuconostoc citreum [L. citreum]) | cell therapies | FDA | 2022-12-01 | — | LISCure Biosciences Inc. |
3-([3,3-dibutyl-7-(methylsulfanyl)-1,1-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1Lambda6,2,5-benzothiadiazepin-8-yl]oxy)propanoic acid | small molecules | FDA | 2022-11-15 | — | Albireo AB |
Bezafibrate | small molecules | EMA | 2022-08-10 | — | Amsterdam UMC |
Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu- Gly-Pro-Pro-Pro-Ala-Leu-Ala-Leu-Ala-NH2 | peptides | FDA | 2022-05-24 | — | Sterotherapeutics, LLC |
Bexotegrast | small molecules | EMA | 2022-04-13 | — | Pharma Gateway AB |
Beta-Lapachone | small molecules | FDA | 2022-03-28 | — | Curome Biosciences Co., Ltd. |
Chimeric peptide of human glucagon-like peptide-1, glucagon and gastric inhibitory polypeptide analogues linked to a human immunoglobulin Fc fragment | proteins | EMA | 2021-12-10 | — | JVM Europe B.V. |
3-(4-((3-endo)-3-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4- yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-2-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one | small molecules | FDA | 2021-09-13 | — | Cascade Pharmaceuticals, Inc |
Norucholic acid | small molecules | FDA | 2021-06-24 | — | Dr. Falk Pharma GmbH |
Humanised IgG1 monoclonal antibody against human eotaxin-2 | antibodies | EMA | 2020-08-21 | — | FGK Representative Service GmbH |
Glucagon-like peptide-1/Glucagon/Gastric inhibitory polypeptide triple agonist linked to human IgG4 Fc fragment | peptides | FDA | 2020-03-04 | — | Hanmi Pharmaceutical Company, Ltd. |
Cilofexor trometamol | small molecules | EMA | 2019-04-01 | — | Gilead Sciences Ireland Unlimited Company |
small molecule inhibitor of integrins avEszett6 and avEszett1 | small molecules | FDA | 2018-11-19 | — | Pliant Therapeutics, Inc. |
2-[3-(2-chloro-4-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}phenyl)-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid¿2-amino-2-(hydroxymethyl)propane-1,3-diol (1/1) | small molecules | FDA | 2018-10-25 | — | Gilead Sciences, Inc. |
Monoclonal antibody targeting CCL24 | antibodies | FDA | 2018-10-11 | — | ChemomAb, Ltd. |
(S)-3-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid | small molecules | EMA | 2017-10-16 | — | Pharma Gateway AB |
5-cholesten-3ß, 25-diol 3-sulfate sodium salt (25HC3S) | small molecules | FDA | 2017-07-06 | — | DURECT Corporation |
(S)-3-((S)-2-(2-((2,6-difluorophenyl)amino)-2-oxoacetamido)propanamido-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid | small molecules | FDA | 2017-06-21 | — | Conatus Pharmaceuticals |
Cotsiranib | RNAs | FDA | 2017-06-15 | — | Sirnaomics, Inc. |
berberine ursodeoxycholate | small molecules | FDA | 2016-08-29 | — | HighTide Therapeutics (Hong Kong) Limited |
recombinant, fully-human, IgG4 immunoglobulin with antigen-binding specificity for human vascular adhesion protein-1 (VAP-1) | antibodies | FDA | 2016-08-25 | — | Acorda Therapeutics, Inc. |
Aldafermin | proteins | EMA | 2015-12-14 | — | Propharma Group The Netherlands B.V. |
Recombinant human monoclonal antibody binding to vascular adhesion protein-1 | antibodies | EMA | 2015-03-19 | — | Biotie Therapies Oy |
simtuzumab | antibodies | FDA | 2015-01-05 | — | Gilead Sciences, Inc. |
docosahexaenoic acid, DHA | small molecules | FDA | 2014-12-17 | — | Micelle BioPharma, Inc. |
Norursodeoxycholic acid | small molecules | EMA | 2014-07-04 | — | Dr Falk Pharma GmbH |
Obeticholic acid [Ocaliva] | small molecules | EMA | 2014-01-16 | — | [INACTIVE] Intercept Pharma International Limited |
Maralixibat chloride | small molecules | EMA | 2013-12-18 | — | Mirum Pharmaceuticals International B.V. |
(4R,5R)-1-[[4-[[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]methyl]phenyl]methyl]-4-aza-l-azoniabicyclo[2.2.2]octane Chloride | small molecules | FDA | 2013-09-04 | — | Mirum Pharmaceuticals, Inc. |
6-alpha-ethylchenodeoxycholic acid | small molecules | FDA | 2008-04-09 | — | Intercept Pharmaceuticals, Inc. |