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 Fabry patient with moderate or severe renal impairment with an eGFR less than 60 mL/min/1.73 m 2 and with a HEK assay amenable α-galactosidase A mutation, 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 the administration is effective to (i) reduce a mean plasma globotriaosylsphingosine (lyso-Gb3) in the patient, and (ii) provide a mean annualized rate of change in eGFR CKD-EPI of greater than −1.0 mL/min/1.73 m 2 .
2. The method of claim 1 , wherein the patient has an eGFR of 30 to 59 mL/min/1.73 m 2 .
3. The method of claim 1 , wherein the patient has an eGFR of 35 to 59 mL/min/1.73 m 2 .
4. The method of claim 1 , wherein the patient has an eGFR of less than 30 mL/min/1.73 m 2 .
5. The method of claim 1 , wherein the patient has an eGFR of 15 to 29 mL/min/1.73 m 2 .
6. 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.
7. 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.
8. 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.
9. The method of claim 1 , wherein the migalastat is in a solid dosage form.
10. The method of claim 1 , wherein the migalastat is administered orally.
11. The method of claim 1 , wherein the migalastat is administered for at least 28 days.
12. The method of claim 1 , wherein the migalastat is administered for at least 6 months.
13. The method of claim 1 , wherein the migalastat is administered for at least 12 months.
14. The method of claim 1 , comprising administering about 123 mg FBE of migalastat.
15. The method of claim 1 , comprising administering about 123 mg of migalastat free base.
16. The method of claim 1 , comprising administering about 150 mg of migalastat hydrochloride.
17. The method of claim 1 , wherein the patient has an eGFR of 30 to 59 mL/min/1.73 m 2 , and wherein the administration is effective to provide a mean reduction in plasma lyso-Gb3 of about 29.0 nmol/L.
18. 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.
19. The method of claim 1 , wherein the migalastat is administered as a pharmaceutically acceptable salt.
20. The method of claim 1 , wherein the patient is an enzyme replacement therapy (ERT)-naïve patient.