Drug discovery
9
drugs
With orphan designations
Overview
Progressive Familial Intrahepatic Cholestasis (PFIC) is a group of rare autosomal recessive disorders caused by defects in hepatobiliary transport proteins (ATP8B1, ABCB11, or ABCB4), leading to impaired bile formation, cholestasis, and progressive liver injury. Clinical hallmarks include severe pruritus, jaundice, failure to thrive, and fat-soluble vitamin deficiencies. Untreated, PFIC progresses to cirrhosis and liver failure, often requiring transplantation. Diagnosis involves genetic testing, serum bile acid profiling, and liver histology [1][2][14].
Burden
Severe pruritus causes sleep disturbances, skin mutilation, and impaired cognitive/social development [4][7][15].
50–87% progress to liver failure before adulthood, often requiring transplantation [1][10][18].
Caregiver burden: Reduced quality of life, financial strain, and emotional distress due to complex care needs [4][15][17].
Therapies
Pharmacologic: Ursodeoxycholic acid (first-line), ileal bile acid transporter (IBAT) inhibitors (odevixibat, maralixibat) [3][12][19], rifampicin, and cholestyramine [16].
Surgical: Partial external biliary diversion (PEBD) for pruritus relief; liver transplantation for end-stage disease [1][8][16].
Supportive: Fat-soluble vitamin supplementation, medium-chain triglycerides [16][18].
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare transplant-related disorders
Drug Discovery Landscape
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
modified human ATP binding cassette subfamily B member 4 (ABCB4) mRNA encoding multidrug resistance protein 3 (MDR3) | RNAs | FDA | 2024-11-18 | — | INNORNA USA INC. |
modified human ATP binding cassette subfamily B member 11 (ABCB11) messenger RNA encoding bile salts export pump | RNAs | FDA | 2024-07-29 | — | INNORNA USA INC. |
3alpha,6beta,7beta,12alpha-tetrahydroxy-5beta-cholan-24-oic acid | small molecules | FDA | 2020-10-22 | — | Qing Bile Therapeutics, Inc. |
Adeno-associated viral vector serotype 3B encoding human multidrug resistance protein 3A | gene therapies | EMA | 2020-04-22 | — | Vivet Therapeutics S.A.S. |
Adeno-associated viral vector encoding human multidrug resistance protein 3A (MDR3A) | gene therapies | FDA | 2020-03-16 | — | Vivet Therapeutics SAS |
(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-1-azoniabicyclo[2.2.2]octane chloride [Livmarli] | small molecules | EMA | 2013-12-18 | 2024-07-01 | Mirum Pharmaceuticals International B.V. |
maralixibat [Livmarli] | small molecules | FDA | 2013-09-04 | 2024-03-13 | Mirum Pharmaceuticals, Inc. |
odevixibat [Bylvay] | small molecules | FDA | 2012-10-31 | 2021-07-20 | Ipsen Biopharmaceuticals, Inc. |
(2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro- 1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid [Bylvay] | small molecules | EMA | 2012-07-17 | 2021-07-19 | Ipsen Pharma |