Claims for Patent: 11,844,756

Summary for Patent: 11,844,756

Title:	Compositions and methods for treating anemia
Abstract:	Provided herein are specific doses of, and dosing regimens for, using a HIF prolyl hydroxylase inhibitor in treating or preventing anemia, such as anemia secondary to or associated with chronic kidney disease, anemia secondary to or associated with non-dialysis dependent chronic kidney disease anemia associated with or resulting from chemotherapy, or anemia associated with AIDS.
Inventor(s):	Alexander Smith, Gurudatt Ajay Chandorkar, Ene Ikpong Ette, Bradley John Maroni, Charlotte Suzanne Hartman, Ramin Farzaneh-Far, Jula Kern Inrig
Assignee:	Akebia Therapeutics Inc
Application Number:	US17/712,709
Patent Claims:	1. A method for treating anemia comprising administering to a patient a formulation comprising intra-granular components, extra-granular components, and film coating components, wherein the intra-granular components comprise about 60% to about 70% by weight of Compound 1: about 20% to about 30% by weight of microcrystalline cellulose, about 2.5% to about 3.5% by weight of sodium starch glycolate, and about 2.3% to about 3.3% by weight of a hydroxypropyl methylcellulose; the extra-granular components comprise: about 2.5% to about 3.5% by weight of a sodium starch glycolate, about 0.2% to about 0.3% by weight of colloidal silicon dioxide, and about 0.55% to about 0.95% by weight of magnesium stearate; the film coating component comprises about 1.0% to about 8% by weight of a tablet coating; and wherein the weight is the total weight of all intra-granular and extra-granular components. 2. The method of claim 1, wherein the anemia is anemia secondary to non-dialysis dependent chronic kidney disease. 3. A method of treating a anemia secondary to non-dialysis dependent chronic kidney disease, comprising administering a sufficient number of successive doses of a formulation comprising intra-granular components, extra-granular components, and film coating components to a patient having anemia secondary to non-dialysis dependent chronic kidney disease wherein the intra-granular components of the formulation comprise: about 60% to about 70% by weight of Compound 1, about 20% to about 30% by weight of microcrystalline cellulose, about 2.5% to about 3.5% by weight of sodium starch glycolate, and about 2.3% to about 3.3% by weight of a hydroxypropyl methylcellulose; the extra-granular components of the formulation comprise: about 2.5% to about 3.5% by weight of a sodium starch glycolate, about 0.2% to about 0.3% by weight of colloidal silicon dioxide, and about 0.55% to about 0.95% by weight of magnesium stearate; the film coating component of the formulation comprises about 1.0% to about 8% by weight of a tablet coating; and wherein the weight is the total weight of all intra-granular and extra-granular components of the formulation; and wherein the patient has at least 2, 3, 4, 5 or all of (i) an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2, wherein the subject is not on dialysis and not expected to start dialysis within 3 months of beginning of treatment, (ii) a hemoglobin level of less than 10.0 g/dL prior to commencement of treatment, (iii) a ferritin level equal to or above 100 ng/mL within 4 weeks of commencement of treatment, (iv) a transferrin saturation (TSAT) level equal to or above 20% within 4 weeks commencement of treatment, (v) a folate measurement equal to or above the lower limit of normal within 4 weeks commencement of treatment, (vi) a vitamin B12 measurement equal to or above the lower limit of normal within 4 weeks commencement of treatment, and (vii) an age of at least 18 years; or wherein the patient has at least 2, 3, 4, 5 or all of (i) an estimated glomerular filtration rate (eGFR) of less than 65 mL/min/1.73 m2, wherein the subject is not on dialysis and not expected to start dialysis within 3 months of beginning of treatment, (ii) a hemoglobin level of less than 10.0 g/dL prior to commencement of treatment, (iii) a ferritin level equal to or above 50 ng/mL within 4 weeks of commencement of treatment, (iv) a transferrin saturation (TSAT) level equal to or above 15% within 4 weeks commencement of treatment, (v) a folate measurement equal to or above the lower limit of normal within 4 weeks commencement of treatment, (vi) a vitamin B12 measurement equal to or above the lower limit of normal within 4 weeks commencement of treatment, and (vii) an age of at least 18 years. 4. A method for treating anemia in a patient having non-dialysis dependent chronic kidney disease comprising: administering to the patient an initial daily dose of Compound 1, as a formulation comprising intra-granular components, extra-granular components, and film coating components, wherein; the intra-granular components of the formulation comprise: about 60% to about 70% by weight of Compound 1, about 20% to about 30% by weight of microcrystalline cellulose, about 2.5% to about 3.5% by weight of sodium starch glycolate, and about 2.3% to about 3.3% by weight of a hydroxypropyl methylcellulose; the extra-granular components of the formulation comprise: about 2.5% to about 3.5% by weight of a sodium starch glycolate, about 0.2% to about 0.3% by weight of colloidal silicon dioxide, and about 0.55% to about 0.95% by weight of magnesium stearate; the film coating component of the formulation comprises about 1.0% to about 8% by weight of a tablet coating; and wherein the weight is the total weight of all intra-granular and extra-granular components of the formulation; and wherein: if the Hgb has not increased by more than 0.5 g/dL above the baseline value after 4 weeks of daily administration at the initial daily dose of Compound 1, increasing the daily dose by 150 mg/day of Compound 1, and increasing the daily dose by 150 mg/day every 4 weeks until Hgb is above 10.0 g/dL; if the Hgb rises rapidly during treatment, reducing the daily dose by 150 mg/day; if the Hgb falls below 10.0 g/dL, increasing the daily dose by 150 mg/day; if the Hgb level exceeds 11.0 g/dL, interrupting treatment until the Hgb decreases to 10.5 g/dL or less, and thereafter resuming daily dosing with a daily dose reduced by 150 mg/day; and if a dose adjustment is required to maintain Hgb at the desired level, adjusting the daily dose by 150 mg/day; or wherein: if the Hgb has not increased by more than 0.5 g/dL above the baseline value after 4 weeks of daily administration at the initial daily dose of Compound 1, increasing the daily dose by 150 mg/day of Compound 1, and increasing the daily dose by 150 mg/day every 4 weeks until Hgb is above 10.0 g/dL; if the Hgb rises rapidly during treatment, reducing the daily dose by 150 mg/day; if the Hgb falls below 10.0 g/dL, increasing the daily dose by 150 mg/day; if the Hgb level exceeds 12.0 g/dL, reducing the daily dose by 150 mg/day, and if Hgb level exceeds 13.0 g/dL, interrupting treatment until the Hgb decreases to 12.5 g/dL or less, and thereafter resuming daily dosing with a daily dose reduced by 150 mg/day; and if a dose adjustment is required to maintain Hgb at the desired level, adjusting the daily dose by 150 mg/day; or wherein: if a dose adjustment is required to maintain Hgb at the desired level, adjusting the daily dose by 150 mg/day; if the Hgb rises rapidly during treatment, reducing the daily dose by 150 mg/day; if the Hgb falls below 10.0 g/dL, increasing the daily dose by 150 mg/day; and if the Hgb level exceeds 11.0 g/dL, interrupting treatment until the Hgb decreases to 10.5 g/dL or less, and thereafter resuming dosing with a daily dose reduced by 150 mg/day. 5. A method for treating anemia in a patient having non-dialysis dependent chronic kidney disease comprising: administering to the patient an initial daily dose of Compound 1, as a formulation comprising intra-granular components, extra-granular components, and film coating components, wherein: the intra-granular components of the formulation comprise: about 60% to about 70% by weight of Compound 1, about 20% to about 30% by weight of microcrystalline cellulose, about 2.5% to about 3.5% by weight of sodium starch glycolate, and about 2.3% to about 3.3% by weight of a hydroxypropyl methylcellulose; the extra-granular components of the formulation comprise: about 2.5% to about 3.5% by weight of a sodium starch glycolate, about 0.2% to about 0.3% by weight of colloidal silicon dioxide, and about 0.55% to about 0.95% by weight of magnesium stearate; the film coating component of the formulation comprises about 1.0% to about 8% by weight of a tablet coating; and wherein the weight is the total weight of all intra-granular and extra-granular components of the formulation; and wherein: if the Hgb has not increased by more than 0.5 g/dL above the baseline value after 4 weeks of daily administration at the initial daily dose of Compound 1, increasing the daily dose by 150 mg/day of Compound 1, and increasing the daily dose by 150 mg/day every 4 weeks until Hgb is above 10.0 g/dL; if the Hgb rises rapidly during treatment, reducing the daily dose by 150 mg/day; if the Hgb falls below 10.0 g/dL, increasing the daily dose by 150 mg/day; if the Hgb level exceeds 12.0 g/dL, reducing the daily dose by 150 mg/day, and if Hgb level exceeds 13.0 g/dL, interrupting treatment until the Hgb decreases to 12.5 g/dL or less, and thereafter resuming daily dosing with a daily dose reduced by 150 mg/day; and if a dose adjustment is required to maintain Hgb at the desired level, adjusting the daily dose by 150 mg/day. 6. The method of claim 4, wherein the baseline value is determined immediately prior to the first administration of Compound 1. 7. The method of claim 4, wherein the Hgb rises rapidly if the Hgb rises more than 1.0 g/dL in any 2-week period. 8. The method of claim 4, wherein the maximum daily dose is 600 mg/day. 9. The method of claim 4, wherein the daily dose is not increased more frequently than once every 4 weeks during the course of treatment. 10. The method of claim 4, wherein the daily dose is decreased more frequently than once every 4 weeks during the course of treatment. 11. The method of claim 4, wherein the initial daily dose is 300 mg/day. 12. The method of claim 11, wherein the initial daily dose is administered in form of two tablets of 150 mg of Compound 1 each. 13. The method of claim 4, wherein the initial daily dose is 450 mg/day. 14. The method of claim 13, wherein the initial daily dose is administered in form of three tablets of 150 mg of Compound 1 each. 15. The method of claim 12, wherein the initial daily dose is administered in the morning. 16. The method of claim 12, wherein the initial daily dose is administered between 7 am and 2 pm. 17. The method of claim 1, wherein the anemia is anemia secondary to or associated with chronic kidney disease. 18. The method of claim 17, wherein the patient is a dialysis patient.