Claims for Patent: 12,409,186

Summary for Patent: 12,409,186

Title:	Methods of treating chronic kidney disease with dapagliflozin
Abstract:	The present disclosure is directed to methods of treating patients with chronic kidney disease (CKD), with and without Type 2 diabetes, with an SGLT2 inhibitor, such as dapagliflozin.
Inventor(s):	Anna Maria LANGKILDE
Assignee:	AstraZeneca AB
Application Number:	US17/219,992
Patent Claims:	1. A method of treating a patient with chronic kidney disease at risk of progression, comprising administering once daily to the patient a pharmaceutical composition comprising a therapeutically effective amount of dapagliflozin, wherein the patient does not have type II diabetes, wherein dapagliflozin is administered for at least four months, and wherein the method reduces a risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), cardiovascular (CV) death, and hospitalization for heart failure in the patient relative to a dosing regimen in which the patient receives no dapagliflozin. 2. The method of claim 1, wherein the sustained decline in eGFR is ≥50%. 3. The method of claim 1, wherein end-stage kidney disease comprises sustained eGFR <15 mL/min/1.73 m2, initiation of chronic dialysis treatment, and/or renal transplant. 4. The method of claim 1, wherein prior to the administration, the patient had (i) an eGFR ≥25 and ≤75 mL/min/1.73 m2; and/or (ii) a urine albumin creatinine ratio (UACR) ≥200 and ≤5000 mg/g. 5. The method of claim 1, wherein (i) prior to the administration, the patient was receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB); and/or (ii) during the administration, the patient is also administered an ACEi or an ARB. 6. The method of claim 5, wherein the angiotensin-converting enzyme inhibitor (ACEi) is chosen from captopril, enalapril, and lisinopril. 7. The method of claim 5, wherein the angiotensin receptor blocker (ARB) is chosen from valsartan, losartan, and irbesartan. 8. The method of claim 1, wherein the patient does not have autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis; and/or the patient has not received cytotoxic, immunosuppressive, or immunomodulatory therapies within 6 months prior to the administration. 9. The method of claim 1, wherein (i) prior to the administration, the patient was administered an antiplatelet agent; and/or (ii) during the administration, the patient is also administered an antiplatelet agent. 10. The method of claim 1, wherein (i) prior to the administration, the patient was administered a statin; and/or (ii) during the administration, the patient is also administered a statin. 11. The method of claim 1, wherein the patient is not on chronic dialysis. 12. A method of treating chronic kidney disease (CKD), comprising administering once daily to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of dapagliflozin, wherein the patient does not have type II diabetes, wherein dapagliflozin is administered for at least four months, wherein the method reduces a risk of an incidence of a composite endpoint in the patient relative to a dosing regimen in which the patient receives no dapagliflozin; and wherein the composite endpoint is ≥50% sustained decline in estimated glomerular filtration rate (eGFR), progression to end-stage kidney disease (ESKD), and CV or renal death. 13. The method of claim 12, wherein end-stage kidney disease comprises sustained eGFR <15 mL/min/1.73 m2, initiation of chronic dialysis treatment, and/or renal transplant. 14. The method of claim 12, wherein prior to the administration, the patient had (i) an eGFR ≥25 and ≤75 mL/min/1.73 m2; and/or (ii) a urine albumin creatinine ratio (UACR) ≥200 and ≤5000 mg/g. 15. The method of claim 12, wherein (i) prior to the administration, the patient was receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB); and/or (ii) during the administration, the patient is also administered an ACEi or an ARB. 16. The method of claim 15, wherein the angiotensin-converting enzyme inhibitor (ACEi) is chosen from captopril, enalapril, and lisinopril. 17. The method of claim 15, wherein the angiotensin receptor blocker (ARB) is chosen from valsartan, losartan, and irbesartan. 18. The method of claim 12, wherein the method satisfies at least one of the following conditions: a) the method results in a hazard ratio for time to first event in the composite endpoint that is less than one relative to a dosing regimen in which the patient receives no dapagliflozin; b) the method results in a hazard ratio for time to first event in the composite endpoint that is statistically nominally less than one relative to a dosing regimen in which the patient receives no dapagliflozin; c) the method results in a hazard ratio for time to first event in the composite endpoint of approximately 0.61 relative to a dosing regimen in which the patient receives no dapagliflozin; d) the method results in a 95% confidence interval for the hazard ratio for time to first event in the composite endpoint of approximately 0.51 to 0.72 relative to a dosing regimen in which the patient receives no dapagliflozin; e) the method numerically reduces the absolute risk of the composite endpoint relative to a dosing regimen in which the patient receives no dapagliflozin; f) the method results in a nominally significant risk reduction of the composite endpoint relative to a dosing regimen in which the patient receives no dapagliflozin; g) the method results in a numerical reduction in the composite endpoint relative to a dosing regimen in which the patient receives no dapagliflozin; h) the method results in a hazard ratio for time to first event in a composite endpoint of CV death and hospitalization for heart failure of approximately 0.71 relative to a dosing regimen in which the patient receives no dapagliflozin; i) the method results in a hazard ratio for time to death from all causes of approximately 0.69 relative to a dosing regimen in which the patient receives no dapagliflozin; j) the method results in a hazard ratio for time to ≥50% sustained decline in estimated glomerular filtration rate (eGFR) of approximately 0.53 relative to a dosing regimen in which the patient receives no dapagliflozin; k) the method results in a hazard ratio for time to cardiovascular (CV) death of approximately 0.81 relative to a dosing regimen in which the patient receives no dapagliflozin; l) the method results in a hazard ratio for time to end stage kidney disease of approximately 0.64 relative to a dosing regimen in which the patient receives no dapagliflozin; and/or m) the method results in a 95% confidence interval for the hazard ratio for time to first event in the composite endpoint of approximately 0.61 with a p-value of <0.0001 relative to a dosing regimen in which the patient receives no dapagliflozin. 19. The method of claim 12, wherein the patient does not have autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis; and/or the patient has not received cytotoxic, immunosuppressive, or immunomodulatory therapies within 6 months prior to the administration. 20. The method of claim 12, wherein (i) prior to the administration, the patient was administered an antiplatelet agent; and/or (ii) during the administration, the patient is also administered an antiplatelet agent. 21. The method of claim 12, wherein (i) prior to the administration, the patient was administered a statin; and/or (ii) during the administration, the patient is also administered a statin. 22. The method of claim 12, wherein the patient is not on chronic dialysis.