METHODS FOR TREATING PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

1 . A method for treating a progressive familial intrahepatic cholestasis (PFIC) in a subject in need thereof comprising administering to the subject maralixibat, or a pharmaceutically acceptable salt thereof, wherein the maralixibat or pharmaceutically acceptable salt thereof is administered in an amount from about 600 μg/kg/day to about 1200 μg/kg/day.

2 . The method of claim 1 , wherein the pharmaceutically acceptable salt of maralixibat is maralixibat chloride, maralixibat bromide, maralixibat acetate, or maralixibat mesylate.

3 . The method of claim 1 , wherein the pharmaceutically acceptable salt of maralixibat is maralixibat chloride.

4 .- 6 . (canceled)

7 . The method of claim 1 , wherein the maralixibat or pharmaceutically acceptable salt thereof is maralixibat chloride, and maralixibat chloride is administered in an amount of about 1200 μg/kg/day.

8 . (canceled)

9 . The method of claim 1 , wherein the PFIC is PFIC 1, PFIC 2, PFIC 3, PFIC 4, PFIC 5, or PFIC 6.

10 .- 17 . (canceled)

18 . The method of claim 1 , wherein the PFIC is heterozygous.

19 . The method of claim 1 , wherein the subject has intermittent cholestasis and/or has undergone biliary diversion surgery.

20 . (canceled)

21 . The method of claim 1 , wherein the subject is a pediatric subject.

22 . (canceled)

23 . (canceled)

24 . The method of claim 1 , wherein the subject has a mutation in a gene selected from the group consisting of: ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, and MYO5B.

25 . The method of claim 24 , wherein the mutation is selected from a non-truncating mutation and a truncating mutation.

26 . (canceled)

27 . The method of claim 1 , wherein the subject has a truncated B SEP protein.

28 . (canceled)

29 . The method of claim 1 , wherein the maralixibat or pharmaceutically acceptable salt thereof is administered twice daily (BID).

30 . The method of claim 1 , wherein the maralixibat or pharmaceutically acceptable salt thereof is maralixibat chloride, and maralixibat chloride is administered at 600 μg/kg/day BID for a total daily dose of 1200 μg/kg/day.

31 .- 36 . (canceled)

37 . The method of claim 1 , wherein the administration of the maralixibat reduces intensity of pruritus as measured by an ItchRO(Obs) score or a CSS score by at least 1.0 points relative to baseline.

38 .- 46 . (canceled)

47 . The method of claim 1 , wherein the administration of the maralixibat or pharmaceutically acceptable salt thereof improves sleep as measured by a reduction of an EDQ(Obs) or EDQ(Pt) score of the subject by at least 1.0 points relative to baseline.

48 .- 53 . (canceled)

54 . The method of claim 1 , wherein the administration of the maralixibat or pharmaceutically acceptable salt thereof reduces total bilirubin and/or direct bilirubin by at least 0.2 mg/dL relative to baseline.

55 .- 66 . (canceled)

67 . The method of claim 1 , wherein the maralixibat or pharmaceutically acceptable salt thereof is administered BID, about 30 minutes before the morning meal and about 30 minutes before the evening meal.

68 . The method of claim 1 , wherein the maralixibat is administered in the form of a pharmaceutical composition comprising maralixibat, or a pharmaceutically acceptable salt thereof, an antioxidant, and a preservative.

69 . The method of claim 68 , wherein the pharmaceutical composition is a liquid composition for oral administration.

70 .- 74 . (canceled)

75 . The method of claim 1 , wherein the preservative is an antimicrobial preservative selected from the group consisting of propylene glycol, ethyl alcohol, glycerin, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, butylparaben, cetrimide (cetyltrimethylammonium bromide), cetrimonium bromide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, cresol, ethylparaben, methylparaben, phenol, phenoxy ethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, propylparaben, sodium benzoate, sodium dehydroacetate, sodium propionate, sorbic acid, potassium sorbate, thimerosal, thymol, and combinations thereof.

76 .- 80 . (canceled)

81 . The method of claim 68 , wherein the antioxidant is an aminopolycarboxylic acid selected from ED TA (ethylene diaminetetraacetic acid), DTPA (diethylenetriaminepentaacetic acid), EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid), NTA (nitrilotriacetic acid), BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid), NOTA (2,2′,2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid), DOTA (tetracarboxylic acid), and EDDHA (ethylenediamine-N,N′-bis(2-hydroxyphenylacetic acid).

82 .- 84 . (canceled)

85 . The method of claim 68 , wherein the pharmaceutical composition comprises:

a. from about 8 mg/mL to about 20 mg/mL of maralixibat;

b. from about 330 mg/mL to about 380 mg/mL of propylene glycol;

c. about 1 mg/mL of disodium EDTA;

d. a sweetener, a taste-masking ingredient, or a combination thereof, and

e. water.