JP-2025517355-A5 -

Dates

Publication Date

20260511

Application Date

20230518

Description

Example 2: Phase 2 open-label basket study of atrasentan in patients with proteinuric glomerular disease. A phase 2 open-label basket study of atrasentan was completed in patients with proteinuric glomerular disease as described in Example 1. Twelve patients with FSGS were enrolled in the study, provided they met the inclusion and exclusion criteria of Example 1. Baseline characteristics of this cohort are shown in Figure 3. Patients were administered 0.75 mg of atrasentan once daily. Declines in the urinary protein-to-creatinine ratio (UPCR) were observed at least 6, 12, and 24 weeks after the start of the study. For example, a 38.3% decrease in UPCR was observed at week 24 compared to the baseline measurement at week 0 (Figure 4). The present specification includes the following embodiments. Item 1: A method for treating focal segmental glomerulosclerosis (FSGS) in a subject, comprising administering a therapeutically effective amount of atrasentan or a pharmaceutically acceptable salt thereof to the subject. Item 2: A method for reducing nephritis and/or fibrosis in a subject having FSGS, comprising administering a therapeutically effective amount of atrasentan or a pharmaceutically acceptable salt thereof to a subject in need. Item 3: A method for reducing the rate of decline in estimated glomerular filtration rate (eGFR) in subjects with FSGS, comprising administering a therapeutically effective dose of atrasentan or a pharmaceutically acceptable salt thereof to a subject in need. Item 4: A method for delaying the onset of end-stage renal disease (ESKD) in subjects with FSGS, comprising administering a therapeutically effective dose of atrasentan or a pharmaceutically acceptable salt thereof to a subject in need. Item 5: A method for reducing proteinuria in a subject having FSGS, comprising administering a therapeutically effective dose of atrasentan or a pharmaceutically acceptable salt thereof to the subject in need. Item 6: A method for reducing fatigue in a subject having FSGS, comprising administering a therapeutically effective amount of atrasentan or a pharmaceutically acceptable salt thereof to the subject in need. Item 7: A method for stabilizing the functional podocyte mass in a subject having FSGS, comprising administering a therapeutically effective dose of atrasentan or a pharmaceutically acceptable salt thereof to the subject in need. Item 8: The method according to claim 2, wherein the nephritis and/or fibrosis includes tubulointerstitial inflammation. Item 9: The method according to claim 2 or 8, wherein the nephritis and/or fibrosis includes tubulointerstitial fibrosis. Item 10: The method according to any one of claims 2, 8, or 9, wherein the nephritis and/or fibrosis includes inflammation of the glomeruli. Item 11: The method according to claim 2 or any one of claims 8 to 10, wherein the nephritis and/or fibrosis includes glomerulosclerosis. Item 12: The method according to any one of claims 1 to 10, wherein the subject has FSGS confirmed by biopsy. Item 13: The method according to any one of items 1 to 10, wherein the subject has been diagnosed with FSGS as confirmed by biopsy. Item 14: The method according to any one of items 1 to 10, wherein the subject has a mutation in a podocyte protein. Item 15: The method according to any one of claims 1 to 10, wherein the subject has a mutation in apolipoprotein L1 (APOL1). Item 16: The method according to any one of claims 1 to 10, wherein the subject has a mutation in one or more of APOL1, NPHS1, NPHS2, CD2AP, TRPC6, ACTN4, INF2, MYO1E, ARHGAP24, PLCE1, WT1, LMX1B, COQ6, LAMB2, PAX2, ANLN, and/or CRB2. Item 17: The method according to any one of claims 1 to 16, wherein the FSGS includes nephrotic syndrome. Item 18: The method according to claim 17, wherein the nephrotic syndrome is selected from proteinuria, hypoalbuminemia, hypercholesterolemia, peripheral edema, or any combination thereof. Item 19: The method according to any one of claims 1 to 18, wherein the FSGS is a gate-peripheral FSGS. Item 20: The method according to any one of claims 1 to 18, wherein the FSGS is a glomerular apex type FSGS. Item 21: The method according to any one of claims 1 to 18, wherein the FSGS is a cell-type FSGS. Item 22: The method according to any one of claims 1 to 18, wherein the FSGS is a collapsed type FSGS. Item 23: The method according to any one of claims 1 to 18, wherein the FSGS is a primary FSGS. Item 24: The method according to any one of claims 1 to 18, wherein the FSGS is a non-specific type FSGS (NOS). Item 25: The method according to any one of claims 1 to 18, wherein the FSGS is a virus-related FSGS. Item 26: The method according to item 25, wherein the virus-related FSGS is not an HIV-related FSGS. Item 27: The method according to any one of claims 1 to 18, wherein the FSGS is a toxin-related FSGS. Item 28: The method according to any one of claims 1 to 18, wherein the FSGS is an applicable FSGS. Item 29: The method according to any one