Methods of treating Fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-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.
1. A method of stabilizing renal function in a patient diagnosed with Fabry disease and having moderate renal impairment with an eGFR of 30 to 59 mL/min/1.73 m 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 the subject provides an increase in plasma migalastat AUC 0-∞ of about 1.8-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 α-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)-naïve 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 , wherein administration of the migalastat to a group of patients having moderate renal impairment provides a mean annualized rate of change in eGFR CKD-EPI of greater than −1.0 mL/min/1.73 m 2 .
13. The method of claim 1 , comprising administering about 123 mg FBE of migalastat at a frequency of every other day.
14. The method of claim 1 , comprising administering about 123 mg of migalastat free base at a frequency of every other day.
15. The method of claim 1 , comprising administering about 150 mg of migalastat hydrochloride at a frequency of every other day.
16. 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 μM migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% α-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type α-galactosidase A activity.
17. The method of claim 1 , wherein the migalastat is administered as migalastat free base.
18. The method of claim 1 , wherein the migalastat is administered as a pharmaceutically acceptable salt.
19. A method of stabilizing renal function in patients diagnosed with Fabry disease and having moderate renal impairment with an eGFR of 30 to 59 mL/min/1.73 m 2 , the method comprising:
administering, to a group of Fabry disease patients having moderate renal impairment and a HEK assay amenable α-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 stabilize mean renal function in the patients, and
wherein administration of a single dose of the migalastat is effective to provide a mean plasma migalastat increase in AUC 0-∞ , of about 1.8-fold compared to healthy control subjects.
20. The method of claim 19 , 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 μM migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% α-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type α-galactosidase A activity.
21. The method of claim 19 , wherein the migalastat is administered as migalastat free base.
22. The method of claim 19 , wherein the migalastat is administered as a pharmaceutically acceptable salt.
23. A method of stabilizing renal function in patients diagnosed with Fabry disease and having moderate renal impairment with an eGFR of 30 to 59 mL/min/1.73 m 2 , the method comprising:
administering, to a group of Fabry disease patients having moderate renal impairment and a HEK assay amenable α-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 CKD-EPI of greater than −1.0 mL/min/1.73 m 2 , and
wherein administration of a single dose of the migalastat is effective to provide a mean plasma migalastat increase in AUC 0-∞ , of about 1.8-fold compared to healthy control subjects.
24. The method of claim 23 , wherein the patients are enzyme replacement therapy (ERT)-experienced patients.
25. The method of claim 23 , wherein the patients are enzyme replacement therapy (ERT)-naïve patients.
26. The method of claim 23 , 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 μM migalastat compared to HEK-293 cells without migalastat, is shown to have (1) a relative increase of at least 20% α-galactosidase A activity and (2) an absolute increase of at least 3% of the wild-type α-galactosidase A activity.
27. The method of claim 23 , wherein the migalastat is administered as migalastat free base.
28. The method of claim 23 , wherein the migalastat is administered as a pharmaceutically acceptable salt.