High concentration alpha-glucosidase compositions for the treatment of Pompe disease
View Patent ↗The present application provides for compositions comprising high concentrations of acid α-glucosidase in combination with an active site-specific chaperone for the acid α-glucosidase, and methods for treating Pompe 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 acid α-glucosidase enzyme formulation.
1. A composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL and the active site-specific chaperone is present in a specific amount sufficient to prevent the formation of acid α-glucosidase aggregates.
2. The composition of claim 1 , wherein the acid α-glucosidase enzyme is a recombinant human wild-type acid α-glucosidase.
3. The composition of claim 1 , wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
4. The composition of claim 3 , wherein the active site-specific chaperone is a hydrochloride salt of 1-deoxynojirimycin.
5. The composition of claim 1 , wherein the active site-specific chaperone is n-butyldeoxynojirimycin or a pharmaceutically acceptable salt thereof.
6. The composition of claim 1 , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.
7. The composition of claim 6 , wherein the acid α-glucosidase is present in an amount selected from the group consisting of about 25 mg/mL, about 80 mg/mL, about 115 mg/mL, about 160 mg/mL, about 200 mg/mL and about 240 mg/mL.
8. The composition of claim 1 , wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 mM and about 20 mM.
9. The composition of claim 1 , wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.
10. The composition of claim 1 , wherein the composition is formulated for subcutaneous administration to a subject.
11. The composition of claim 1 , wherein the composition is formulated for intravenous administration to a subject.
12. The composition of claim 1 , further comprising a buffer selected from the group consisting of citrate buffer, acetate buffer, bicarbonate buffer, phosphate buffer and combinations thereof.
13. The composition of claim 1 , further comprising an excipient selected from the group consisting of polyethylene glycol 400, arginine, glutamic acid, proline, gammacyclodextrin and combinations thereof.
14. A method of treating Pompe disease in a subject comprising administering to the subject a composition comprising acid α-glucosidase and an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin and n-butyldeoxynojirimycin, wherein the acid α-glucosidase is present in an amount greater than about 5 mg/mL and the active site-specific chaperone is present in a specific amount sufficient to prevent the formation of acid α-glucosidase aggregates.
15. The method of claim 14 , wherein the active site-specific chaperone is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
16. The method of claim 14 , wherein the acid α-glucosidase is present in an amount between about 5 mg/mL and about 250 mg/mL.
17. The method of claim 14 , wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 0.5 mM and about 20 mM.
18. The method of claim 14 , wherein the active site-specific chaperone is 1-deoxynojirimycin present in an amount between about 20 mg/mL and about 200 mg/mL.
19. The method of claim 14 , wherein the active site-specific chaperone is n-butyldeoxynojirimycin or a pharmaceutically acceptable salt thereof.
20. The method of claim 14 , wherein the composition is administered subcutaneously.