Alpha-galactosidase A and 1-deoxygalactonojirimycin co-formulation for the treatment of fabry disease

Patent metadata

Field	Value
Publication number	US-10155027-B2
Application number	US-201715426583-A
Country	US
Kind code	B2
Filing date	Feb 7, 2017
Priority date	Jul 17, 2012
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present application provides compositions comprising α-galactosidase A in combination with an active site-specific chaperone for the α-galactosidase A, and methods for treating Fabry disease in a subject in need thereof, that includes a method of administering to the subject such compositions. The present application also provides methods for increasing the in vitro and in vivo stability of an α-galactosidase A enzyme formulation. The present application also provides methods for treating Fabry disease using intravenous administration of 1-deoxygalactonojirimycin.

First claim

What is claimed is:

1. A method of treating Fabry disease in a subject, the method comprising intravenously administering to the subject a pharmaceutical composition comprising a co-formulation of recombinant human α-galactosidase A and 1-deoxygalactonojirimycin, or a pharmaceutically acceptable salt thereof, wherein the 1-deoxygalactonojirimycin or pharmaceutically acceptable salt thereof is administered at a dosage of about 0.1 to about 15 mg/kg and the recombinant human α-galactosidase A is administered at a dosage of about 0.1 to about 5 mg/kg.

2. The method of claim 1 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is selected from the group consisting of about 0.1, 0.3, 1, 3, and 10 mg/kg.

3. The method of claim 1 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is about 0.3 to about 10 mg/kg.

4. The method of claim 1 , wherein the salt is a hydrochloride salt of 1-deoxygalactonojirimycin.

5. The method of claim 1 , wherein the pharmaceutical composition is administered once per day, once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days.

6. The method of claim 1 , wherein the co-formulation comprises:
about 0.5 to about 20 μM recombinant human α-galactosidase A; and
about 50 to about 20,000 μM 1-deoxygalactonojirimycin or salt thereof.

7. The method of claim 6 , wherein the α-galactosidase A is present at a concentration selected from the group consisting of about 1.2, 2, 4, 8, and 12 μM; and the 1-deoxygalactonojirimycin or salt thereof is present at a concentration selected from the group consisting of about 449, 1,495, 4,490, 5 and 14,950 μM.

8. The method of claim 6 , wherein the 1-deoxygalactonojirimycin and α-galactosidase A are present in a molar ratio of 1-deoxygalactonojirimycin to α-galactosidase A of between about 13,000:1 and about 50:1.

9. The method of claim 6 , wherein the pharmaceutical composition is administered once per day, once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days.

10. The method of claim 1 , wherein the pharmaceutical composition is administered every other week.

11. The method of claim 1 , wherein the dosage of recombinant human α-galactosidase A is about 1 to about 3 mg/kg.

12. A method of treating Fabry disease in a subject, the method comprising intravenously administering to the subject a pharmaceutical composition comprising a co-formulation of recombinant human α-galactosidase A and 1-deoxygalactonojirimycin, or a pharmaceutically acceptable salt thereof, wherein the 1-deoxygalactonojirimycin or pharmaceutically acceptable salt thereof is administered at a dosage of about 0.3 to about 10 mg/kg and the recombinant human α-galactosidase A is administered at a dosage of about 0.1 to about 5 mg/kg, wherein the pharmaceutical composition is administered once every seven days or once every other week.

13. The method of claim 12 , wherein the salt is a hydrochloride salt of 1-deoxygalactonojirimycin.

14. The method of claim 12 , wherein the pharmaceutical composition is administered every other week.

15. The method of claim 12 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is about 0.3 mg/kg.

16. The method of claim 12 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is about 1 mg/kg.

17. The method of claim 12 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is about 3 mg/kg.

18. The method of claim 12 , wherein the dosage of 1-deoxygalactonojirimycin or salt thereof is about 10 mg/kg.

19. The method of claim 12 , wherein the dosage of recombinant human α-galactosidase A is about 1 to about 3 mg/kg.

Assignees

• Amicus Therapeutics Inc

Inventors

• Khanna Richie
• Valenzano Kenneth
• Fowles Susan Elizabeth

Classifications

• A61K38/47 Primary

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C12Y302/01022

  Alpha-galactosidase (3.2.1.22) · CPC title