Granted Patent B2

US 10,874,655 · App. 16/678,183 · Granted Dec 29, 2020

Inventors: Jeff Castelli (New Hope, PA); Elfrida Benjamin (Millstone Township, NJ)

Assignee: Amicus Therapeutics, Inc.

A61K31/445A61P13/12A61K9/48

Abstract

Claims (22)

1. A method of treating Fabry disease in a human patient having moderate renal impairment with an eGFR of 30 to 59 mL/min/1.73 m 2 , the method comprising administering to the patient a therapeutically effective dose of migalastat at a frequency of once every other day, wherein the therapeutically effective dose is about 100 mg to about 150 mg free base equivalent (FBE), wherein the patient has a HEK assay amenable mutation in α-galactosidase A, and wherein the dose is not adjusted relative to a patient without renal impairment.

2. The method of claim 1 , wherein the patient is an enzyme replacement therapy (ERT)-experienced patient.

3. The method of claim 1 , wherein the patient is an enzyme replacement therapy (ERT)-naïve patient.

4. The method of claim 1 , wherein the patient has a proteinuria level of less than 100 mg/24 hr prior to initiating the administration of the migalastat.

5. The method of claim 1 , wherein the patient has a proteinuria level of 100 to 1,000 mg/24 hr prior to initiating the administration of the migalastat.

6. The method of claim 1 , wherein the patient has a proteinuria level of greater than 1,000 mg/24 hr prior to initiating the administration of the migalastat.

7. The method of claim 1 , wherein the migalastat is administered orally.

8. The method of claim 7 , wherein the migalastat is in a solid dosage form.

9. The method of claim 8 , wherein the solid dosage form comprises a capsule.

10. The method of claim 1 , wherein the migalastat is administered for at least 28 days.

11. The method of claim 1 , wherein the migalastat is administered for at least 12 months.

12. The method of claim 1 , wherein administration of the therapeutically effective dose of the migalastat provides an annualized rate of change in eGFR CKD-EPI of greater than −1.0 mL/min/1.73 m 2 .

13. The method of claim 1 , wherein the therapeutically effective dose is about 123 mg FBE.

14. The method of claim 1 , wherein the therapeutically effective dose is about 123 mg of migalastat free base.

15. The method of claim 1 , wherein the therapeutically effective dose is about 150 mg of migalastat hydrochloride.

16. The method of claim 1 , wherein the HEK assay amenable mutation in α-galactosidase A is selected from the group consisting of: L3V, L3P, R4M/Y207S, A13T, A13P, A15T, A15G, F18C, A20D, W24R, W24G, W24C, D33G, N34D, N34T, G35E, G35V, L36S, L36W, A37T, M42K, M42I, H46P, E48Q, N53D, N53L, L54F, Q57L, P60T, P60S, F69L, M721, G80D, D83N, G85S, G85N, E87D, L89F, M961, S102L, G104V, L106F, A108T, D109G, R112G, Y123C, H125L, S126G, G128E, I133M, D136E, N139S, K140T, G144D, F145S, P146S, P146R, Y152H, D165H, D165G, L166G, L167V, C174R, C174G, D175E, L180W, L180F, Y184N, K185E, p.M187_S188dup, M1871, G195V, R196G, I198T, V199A, V199G, Y200C, E203V, E203D, Y207H, M208R, P210S, P210L, K213M, P214S, P214L, N215S/D313Y, I219L, I219T, R220Q, R220P, Q221P, N224T, H225D, N228S, F229L, I232T, I242V, I242F, I242T, W245G, N249K, Q250R, Q250H, I253S, A257G, G258R, G260E, G261S, G261C, M267T, 1270M, G271S/D313Y, G271D, W277G, W277C, T282I, M284V, I289S, M290L, M290I, A291T, L294S, M296L, M296T, D299E, R301L, I303F, S304N, S304T, A307T, A309V, L311V, Q312H, D313Y, D313Y/G411D, V316I, V316G, 1319F, I319T, Q321H, D322N, D322E, P323R, G325R, K326N, Q330R, G334E, F337S, P343L, W349S, A352G, A352V, R356G, R356Q, R356P, E358Q, E358D, G360C, G361E, G361A, P362T, A368T, G375E, T385A, V390M, K391T, G395E, G395A, T412N, E418G and M421V.

17. The method of claim 1 , wherein administration of the provides an about 1.8-fold increase in plasma migalastat AUC 0-∞ in the patient as compared a plasma migalastat AUC 0-∞ in a control subject following administration of a comparable amount of migalastat to the control subject.

18. The method of claim 1 , wherein administration of the migalastat thereof provides no increase in mean plasma migalastat C max in the patient as compared to a plasma migalastat C max in a control subject following administration of a comparable amount of migalastat to the control subject.

19. The method of claim 1 , wherein the patient's eGFR is from 30 to 35 mL/min/1.73 m 2 .

20. The method of claim 1 , wherein the HEK assay amenable mutation in α-galactosidase A is selected from the group consisting of: A13T, A13P, N34D, N34T, G35V, M42K, E48Q, N53L, L54F, P60T, P60S, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, L167V, L180W, K185E, R196G, V199G, Y200C, E203V, E203D, Y207H, M208R, I219L, Q221P, N224T, I242T, Q250R, Q250H, A257G, G261S, G261C, G271D, W277G, W277C, M284V, I303F, A307T, D322N, K326N, G334E, F337S, W349S, A352V, E358Q, E358D, G361E, G375E, G395E, T412N, and M421V.

21. The method of claim 1 , wherein the migalastat is administered as migalastat free base.

22. The method of claim 1 , wherein the migalastat is administered as a pharmaceutically acceptable salt.

Assignments (9)

Cited By (1)

US 12,594,268