Claims for Patent: 10,874,656

Summary for Patent: 10,874,656

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:	16/817,888
Patent Claims:	1. A method of stabilizing renal function in enzyme replacement therapy (ERT)-experienced patients diagnosed with Fabry disease and having renal impairment, the method comprising: administering to a group of Fabry disease patients having 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 (i) increase the mean white blood cell (WBC) .alpha.-galactosidase A activity in the patients, and (ii) provide a mean annualized rate of change in eGFR.sub.CKD-EPI of greater than -1.0 mL/min/1.73 m.sup.2. 2. The method of claim 1, wherein the patients have mild renal impairment with an eGFR of 60 to 90 mL/min/1.73 m.sup.2. 3. The method of claim 1, wherein the patients have moderate renal impairment with an eGFR of 30 to 59 mL/min/1.73 m.sup.2. 4. The method of claim 1, wherein the patients have severe renal impairment with an eGFR of less than 30 mL/min/1.73 m.sup.2. 5. The method of claim 1, wherein the patients have a proteinuria level of less than 100 mg/24 hr prior to initiating the administration of the migalastat. 6. The method of claim 1, wherein the patients have a proteinuria level of 100 to 1,000 mg/24 hr prior to initiating the administration of the migalastat. 7. The method of claim 1, wherein the patients have a proteinuria level of greater than 1,000 mg/24 hr prior to initiating the administration of the migalastat. 8. The method of claim 1, wherein the migalastat is in a solid dosage form. 9. The method of claim 1, wherein the migalastat is administered orally. 10. The method of claim 1, wherein the migalastat is administered for at least 28 days. 11. The method of claim 1, wherein the migalastat is administered for at least 6 months. 12. The method of claim 1, wherein the migalastat is administered for at least 12 months. 13. The method of claim 1, comprising administering about 123 mg FBE. 14. The method of claim 1, comprising administering about 123 mg of migalastat free base. 15. The method of claim 1, comprising administering about 150 mg of migalastat hydrochloride. 16. The method of claim 1, wherein the patients have moderate renal impairment, and wherein the administration is effective to provide a mean increase in WBC .alpha.-galactosidase A activity of about 1.44 MU/hr/mg. 17. The method of claim 1, wherein the patients have mild renal impairment, and wherein the administration is effective to provide a mean increase in WBC .alpha.-galactosidase A activity of about 1.64 MU/hr/mg. 18. The method of claim 1, wherein the HEK assay amenable mutation is a mutation that is shown to have a relative increase of .gtoreq.1.20-fold and an absolute increase of .gtoreq.3.0% wild-type 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. 19. The method of claim 1, wherein the migalastat is administered as migalastat free base. 20. The method of claim 1, wherein the migalastat is administered as a pharmaceutically acceptable salt. 21. A method of stabilizing renal function in a patient diagnosed with Fabry disease and having mild renal impairment with an eGFR of 60 to 90 mL/min/1.73 m2, 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, and increasing white blood cell (WBC) .alpha.-galactosidase A activity in the patient, wherein the administration of the migalastat is effective to stabilize renal function in the patient, wherein the patient has a HEK assay amenable mutation in .alpha.-galactosidase A, wherein the HEK assay amenable mutation is a mutation that is shown to have a relative increase of .gtoreq.1.20-fold and an absolute increase of .gtoreq.3.0% wild-type 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, wherein the patient is an enzyme replacement therapy (ERT)-experienced patient, and wherein the patient has a proteinuria level of 100 to 1,000 mg/24 hr prior to initiating the administration of the migalastat. 22. The method of claim 21, wherein the migalastat is administered as migalastat free base. 23. The method of claim 21, wherein the migalastat is administered as a pharmaceutically acceptable salt.