Granted Patent
B2
US 12,576,079 · App. 17/119,132 · Granted Mar 17, 2026
Methods for treating cholestasis
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Abstract
Provided herein are methods for treating cholestasis in a subject having a liver disease. The method includes administering to the subject an Apical Sodium-dependent Bile Acid Transporter (ASBTI). More specifically, the present invention relates to methods for treating cholestasis in a subject where the method includes administering an ASBTI to a subject at a dose of at least 10 μg/kg/day.
Claims (16)
1 . A method for treating cholestatic liver disease in a subject comprising administering to the subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is
(volixibat), and wherein the volixibat administered in an amount of about 40 mg/day to about 200 mg/day, wherein the administration of the ASBTI reduces sBA concentration by at least 30% by 18 weeks.
2 . The method of claim 1 , wherein the cholestatic liver disease is selected from progressive familial intrahepatic cholestasis (PFIC), Alagille Syndrome (ALGS), primary sclerosing cholangitis (PSC), biliary atresia, intrahepatic cholestasis of pregnancy (ICP), or primary biliary cholangitis (PBC).
3 . The method of claim 1 , wherein the subject is a pediatric subject.
4 . The method of claim 1 , wherein the ASBTI is administered once daily (QD).
5 . The method of claim 1 , wherein the ASBTI is administered twice daily (BID).
6 . The method of claim 1 , wherein the administration of the ASBTI reduces a symptom or changes a disease-relevant laboratory measure of the cholestatic liver disease that is maintained for at least 6 months.
7 . The method of claim 6 , wherein the reduction in the symptom or the change in the disease-relevant laboratory measure comprises a reduction in sBA concentration, an increase in serum 7αC4 concentration, a reduction in pruritis, an increase in a quality of life inventory score, an increase in a quality of life inventory score related to fatigue, a reduction in xanthoma score, an increase in growth, or a combination thereof.
8 . The method of claim 7 , wherein the reduction in the symptom or the change in the disease-relevant laboratory measure is determined relative to a baseline level.
9 . The method of claim 7 , wherein the administration reduces a xanthoma score of the subject by at least 25%.
10 . The method of claim 7 , wherein the administration of the ASBTI increases serum 7αC4 concentration by at least 50% by about 18 weeks.
11 . The method of claim 1 , wherein upon day 7 of administration of the ASBTI the subject's fBA excretion increases by at least 1.5-fold relative to baseline.
12 . The method of claim 1 , wherein administration of the ASBTI increases fBA excretion at least 4-fold relative to baseline.
13 . The method of claim 1 , wherein the cholestatic liver disease is PBC.
14 . The method of claim 1 , wherein the subject is an adult.
15 . The method of claim 1 , wherein the administration of the ASBTI reduces intensity of pruritus.
Assignments (5)
CHANGE OF ADDRESS
Recorded Jun 6, 2024
From: MIRUM PHARMACEUTICALS, INC.
To: MIRUM PHARMACEUTICALS, INC.
Reel/Frame 067643/0852 →
CHANGE OF ADDRESS
Recorded Jul 1, 2022
From: MIRUM PHARMACEUTICALS, INC.
To: MIRUM PHARMACEUTICALS, INC.
Reel/Frame 060559/0428 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2021
From: DORENBAUM, ALEJANDRO
To: SHIRE HUMAN GENETIC THERAPIES, INC.
Reel/Frame 058311/0209 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 6, 2021
From: SHIRE HUMAN GENETIC THERAPIES, INC.
To: MIRUM PHARMACEUTICALS, INC.
Reel/Frame 058320/0798 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 22, 2021
From: JAECKLIN, THOMAS
To: MIRUM PHARMACEUTICALS, INC.
Reel/Frame 057565/0583 →
Continuity (6)
Continuation
PCTUS2020017941
· Feb 12, 2020
Provisional Application
62932015
· Nov 7, 2019
Provisional Application
62908431
· Sep 30, 2019
Provisional Application
62863904
· Jun 20, 2019
Provisional Application
62804523
· Feb 12, 2019
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Presentation slides of Richard Thompson et al., “Journal of Hepatology 70(1):e131-e132” (presented on Apr. 13, 2019), which were published on the Mirum pharmaceuticals website in Jul. 2019, “Growth analysis in children …
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Presentation slides of Emmanuel Gonzales et al., “Journal of Hepatology, Apr. 2019; 70:e119-120” (presented on Apr. 13, 2019), which were published on the Mirum pharmaceuticals website in Jul. 2019, “Phase 2 placebo-con…
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Presentation slides of Richard Thompson, “Hepatology. Oct. 2019; 70(Suppl.1), p. 56A” (presented on Nov. 10, 2019), which were published on the Mirum pharmaceuticals website in Nov. 2019, “Genotype and dose-dependent re…
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Presentation slides of Emmanuel Gonzales, “Hepatology, 2019, 70(6, Suppl,), p. 1479A” (presented on Nov. 11, 2019), which were published on the Mirum pharmaceuticals website in Nov. 2019, “Durability of Treatment Effect…
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Full presentation slides of Richard Thompson, “Hepatology, 2017, vol. 66, No. 6, p. 1255A-1256A” (which was presented in Dec. 2017), which were published on the Mirum pharmaceuticals website in Jul. 2019, “A long-term p…
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Mirum Pharmaceuticals Presents New Data Demonstrating Durable Improvements in Clinical Outcome Measures in Patients with PFIC2 and Alagille Syndrome Treated with Maralixibat, Apr. 15, 2019, 6 pages.
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Clinical Trials.Gov: “Open Label Study to Evaluate Efficacy and Long Term Safety of LUMOOI (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis (INDI…
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Clinical Trials.Gov: A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects with Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC), Clinical Trials.gov ID NCT03905330, 13 pages, Las…
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A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC), (clinical trial NCT03353454, version 2) retrieved from the Internet: URL: <https://clin…
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NCT01903400 is a phase 2 clinical trial titled “A Randomized, Double-blind, Placebo controlled Study to Evaluate the Safety and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in …
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