Claims for Patent: 10,792,278

Summary for Patent: 10,792,278

Title:	Methods of treating Fabry patients having renal impairment
Abstract:	Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in .alpha.-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.
Inventor(s):	Castelli; Jeff (New Hope, PA), Benjamin; Elfrida (Millstone Township, NJ)
Assignee:	Amicus Therapeutics, Inc. (Cranbury, NJ)
Application Number:	16/817,911
Patent Claims:	1. A method of stabilizing renal function in a patient diagnosed with Fabry disease and having severe renal impairment with an eGFR less than 30 mL/min/1.73 m.sup.2, the method comprising: administering to the patient about 100 mg to about 150 mg free base equivalent (FBE) of migalastat at a frequency of once every other day, wherein administration of a single dose of the migalastat to subjects provides an increase in plasma migalastat AUC.sub.0-.infin. of about 4.5-fold compared to a healthy control subject, and wherein the administration of the migalastat is effective to stabilize renal function in the patient and wherein the patient has a HEK assay amenable mutation in .alpha.-galactosidase A. 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)-naive 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 in a solid dosage form. 8. The method of claim 1, wherein the migalastat is administered orally. 9. The method of claim 1, wherein the migalastat is administered for at least 28 days. 10. The method of claim 1, wherein the migalastat is administered for at least 6 months. 11. The method of claim 1, wherein the migalastat is administered for at least 12 months. 12. The method of claim 1, comprising administering about 123 mg FBE of migalastat at a frequency of every other day. 13. The method of claim 1, comprising administering about 123 mg of migalastat free base at a frequency of every other day. 14. The method of claim 1, comprising administering about 150 mg of migalastat hydrochloride at a frequency of every other day. 15. The method of claim 1, wherein the HEK assay amenable mutation is a mutation that, when the mutation is expressed in HEK-293 cells incubated in the presence of 10 .mu.M migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% .alpha.-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type .alpha.-galactosidase A activity. 16. The method of claim 1, wherein the migalastat is administered as migalastat free base. 17. The method of claim 1, wherein the migalastat is administered as a pharmaceutically acceptable salt. 18. A method of stabilizing renal function in patients diagnosed with Fabry disease and having severe renal impairment with an eGFR less than 30 mL/min/1.73 m.sup.2, the method comprising: administering, to a group of Fabry disease patients having severe renal impairment and a HEK assay amenable .alpha.-galactosidase A mutation, about 100 mg to about 150 mg free base equivalent (FBE) of migalastat at a frequency of once every other day, wherein administration of a single dose is effective to provide a mean plasma migalastat increase in AUC.sub.0-.infin. of about 4.5-fold compared to healthy control subjects. 19. The method of claim 18, wherein the HEK assay amenable mutation is a mutation that, when the mutation is expressed in HEK-293 cells incubated in the presence of 10 .mu.M migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% .alpha.-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type .alpha.-galactosidase A activity. 20. The method of claim 18, wherein the migalastat is administered as migalastat free base. 21. The method of claim 18, wherein the migalastat is administered as a pharmaceutically acceptable salt. 22. A method of stabilizing renal function in patients diagnosed with Fabry disease and having severe renal impairment with an eGFR less than 30 mL/min/1.73 m.sup.2, the method comprising: administering, to a group of Fabry disease patients having severe renal impairment and a HEK assay amenable .alpha.-galactosidase A mutation, about 100 mg to about 150 mg free base equivalent (FBE) of migalastat at a frequency of once every other day, wherein the administration is effective to provide a mean annualized rate of change in eGFR.sub.CKD-EPI of greater than -1.0 mL/min/1.73 m.sup.2, and wherein administration of a single dose of the migalastat is effective to provide a mean plasma migalastat increase in AUC.sub.0-.infin. of about 4.5-fold compared to healthy control subjects. 23. The method of claim 22, wherein the patients are enzyme replacement therapy (ERT)-experienced patients. 24. The method of claim 22, wherein the patients are enzyme replacement therapy (ERT)-naive patients. 25. The method of claim 22, wherein the HEK assay amenable mutation is a mutation that, when the mutation is expressed in HEK-293 cells incubated in the presence of 10 .mu.M migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% .alpha.-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type .alpha.-galactosidase A activity. 26. The method of claim 22, wherein the migalastat is administered as migalastat free base. 27. The method of claim 22, wherein the migalastat is administered as a pharmaceutically acceptable salt.