Methods of treating Fabry patients having renal impairment

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Patent No.: US 10,471,053
App. No.: 16/284,582
Granted: Nov 12, 2019
Kind: B2

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Abstract

Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.

Claims (31)

1. A method for treatment of Fabry disease in a human patient in need thereof, the method comprising administering to the patient a therapeutically effective dose of migalastat or a salt thereof, wherein the patient has a HEK assay amenable mutation in α-galactosidase A 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, M72I, G80D, D83N, G85S, G85N, E87D, L89F, M96I, 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, M187I, 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, I270M, 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, I319F, 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.

2. The method of claim 1 , wherein the migalastat or salt thereof is administered to the patient every other day.

3. The method of claim 1 , wherein the patient is administered about 123 to about 300 mg of the migalastat or salt thereof every other day.

4. The method of claim 1 , wherein the patient is administered about 150 mg of the migalastat or salt thereof every other day.

5. The method of claim 1 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

6. The method of claim 1 , wherein the migalastat or salt thereof enhances α-galactosidase A activity.

7. The method of claim 1 , wherein the patient is male.

8. The method of claim 1 , wherein the patient is female.

9. The method of claim 1 , wherein the patient has renal impairment.

10. The method of claim 9 , wherein the patient has mild or moderate renal impairment.

11. The method of claim 1 , wherein the mutation is selected from the group consisting of: L3V, L3P, R4M/Y207S, A13T, A13P, A15T, A15G, F18C, A20D, W24R, W24G, W24C, D33G, N34D, N34T, G35E and G35V.

12. The method of claim 1 , wherein the mutation is selected from the group consisting of: L36S, L36W, A37T, M42K, M42I, H46P, E48Q, N53D, N53L, L54F, Q57L, P60T, P60S, F69L, M72I, G80D and D83N.

13. The method of claim 1 , wherein the mutation is selected from the group consisting of: G85S, G85N, E87D, L89F, M96I, S102L, G104V, L106F, A108T, D109G, R112G, Y123C, H125L, S126G, G128E, I133M, D136E and N139S.

14. The method of claim 1 , wherein the mutation is selected from the group consisting of: K140T, G144D, F145S, P146S, P146R, Y152H, D165H, D165G, L166G, L167V, C174R, C174G, D175E, L180W, L180F, Y184N and K185E.

15. The method of claim 1 , wherein the mutation is selected from the group consisting of: p.M187_S188dup, M187I, G195V, R196G, I198T, V199A, V199G, Y200C, E203V, E203D, Y207H, M208R, P210S, P210L, K213M, P214S, P214L and N215S/D313Y.

16. The method of claim 1 , wherein the mutation is selected from the group consisting of: I219L, I219T, R220Q, R220P, Q221P, N224T, H225D, N228S, F229L, I232T, I242V, I242F, I242T, W245G, N249K, Q250R and Q250H.

17. The method of claim 1 , wherein the mutation is selected from the group consisting of: I253S, A257G, G258R, G260E, G261S, G261C, M267T, I270M, G271S/D313Y, G271D, W277G, W277C, T282I, M284V, I289S, M290L and M290I.

18. The method of claim 1 , wherein the mutation is selected from the group consisting of: A291T, L294S, M296L, M296T, D299E, R301L, I303F, S304N, S304T, A307T, A309V, L311V, Q312H, D313Y, D313Y/G411D, V316I and V316G.

19. The method of claim 1 , wherein the mutation is selected from the group consisting of: I319F, I319T, Q321H, D322N, D322E, P323R, G325R, K326N, Q330R, G334E, F337S, P343L, W349S, A352G, A352V, R356G, R356Q and R356P.

20. The method of claim 1 , wherein the mutation is selected from the group consisting of: E358Q, E358D, G360C, G361E, G361A, P362T, A368T, G375E, T385A, V390M, K391T, G395E, G395A, T412N, E418G and M421V.

21. A method for treatment of Fabry disease in a human patient in need thereof, the method comprising administering to the patient a therapeutically effective dose of migalastat or a salt thereof, wherein the patient has a HEK assay amenable mutation in α-galactosidase A disclosed in a reference table, wherein the reference table includes one or more of the following mutations: 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, M72I, G80D, D83N, G85S, G85N, E87D, L89F, M96I, 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, M187I, 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, I270M, 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, I319F, 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 or M421V.

22. The method of claim 21 , wherein the reference table includes each of the following mutations: 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, M72I, G80D, D83N, G85S, G85N, E87D, L89F, M96I, 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, M187I, 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, I270M, 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, I319F, 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.

23. The method of claim 21 , wherein the migalastat or salt thereof is administered to the patient every other day.

24. The method of claim 21 , wherein the patient is administered about 123 to about 300 mg of the migalastat or salt thereof every other day.

25. The method of claim 21 , wherein the patient is administered about 150 mg of the migalastat or salt thereof every other day.

26. The method of claim 21 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

27. The method of claim 21 , wherein the migalastat or salt thereof enhances α-galactosidase A activity.

28. The method of claim 21 , wherein the patient is male.

29. The method of claim 21 , wherein the patient is female.

30. The method of claim 21 , wherein the patient has renal impairment.

31. The method of claim 30 , wherein the patient has mild or moderate renal impairment.

Assignments (9)

RELEASE OF SECURITY INTEREST Recorded Apr 27, 2026

From: WILMINGTON TRUST, NATIONAL ASSOCIATION