High concentration alpha-glucosidase compositions for the treatment of pompe disease
The present application provides for compositions comprising high concentrations of acid a-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 method of treating Pompe disease in a subject comprising administering
(i) a first composition comprising an active site-specific chaperone selected from the group consisting of 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof and n-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof, and
(ii) a second composition comprising acid α-glucosidase,
wherein the active site-specific chaperone of the first composition is present in an amount from about 20 mg/mL to about 200 mg/mL, and wherein the acid α-glucosidase of the second composition is present in an amount from about 5 mg/mL to about 500 mg/mL.
2. The method of claim 1 , wherein the acid α-glucosidase of the second composition is present in an amount from about 5 mg/mL to about 250 mg/mL.
3. The method of claim 2 , wherein the acid α-glucosidase of the second composition is present in an amount from about 10 mg/mL to about 200 mg/mL.
4. The method of claim 1 , wherein the acid α-glucosidase of the second composition is present in an amount of about 25 mg/mL.
5. The method of claim 1 , wherein at least one of the first composition and the second composition is a liquid formulation.
6. The method of claim 1 , wherein at least one of the first composition and the second composition further comprises an excipient.
7. The method of claim 6 , wherein the excipient is selected from the group consisting of polyethylene glycol 400, arginine, glutamic acid, proline, gammacyclodextrin, and combinations thereof.
8. The method of claim 1 , wherein at least one of the first composition and second composition further comprises a buffer.
9. The method of claim 8 , wherein the buffer is selected from the group consisting of citrate buffer, acetate buffer, bicarbonate buffer, phosphate buffer, and combinations thereof.
10. The method of claim 1 , wherein the active site-specific chaperone of the first composition is n-butyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein the active site-specific chaperone of the first composition is 1-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 , wherein at least one of the first composition and the second composition are administered independently by subcutaneous injections.
13. The method of claim 12 , wherein at least one of the first composition and the second composition are administered independently with separate subcutaneous injections of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 milliliters.
14. The method of claim 1 , wherein at least one of the first composition and the second composition are administered intravenously as separate independent injections.
15. The method of claim 1 , wherein the first composition is administered orally and the second composition is administered intravenously.