# US 12,213,988 B2 · Methods of treating chronic kidney disease with dapagliflozin

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- Number: US 12,213,988 B2
- Document ID: US12213988B2
- Status: Granted
- Kind: B2
- Application number: 17/347,230
- Filed: 2021-06-14
- Published: 2022-01-27
- Granted: 2025-02-04
- Earliest claimed: 2020-07-27
- Assignees: AstraZeneca AB
- Applicants: Astrazeneca AB
- Inventors: Anna Maria Langkilde
- Web page: https://patentgrep.com/patent/US12213988B2

## CPC

- A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047)
- A61K 31/7004: Monosaccharides having only carbon, hydrogen and oxygen atoms
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 31/351: not condensed with another ring
- A61K 31/401: Proline; Derivatives thereof, e.g. captopril
- A61K 31/41: having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 13/12: of the kidneys
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## 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.

## Claims

### Claim 1

A method for treating a patient with chronic kidney disease at risk of progression, the method comprising:
administering dapagliflozin once daily to the patient at a dose and duration sufficient to reduce the patient's risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), cardiovascular (CV) death, and hospitalization for heart failure;
wherein the patient does not have type II diabetes; and
wherein the duration is at least four months.

### Claim 2 (depends on 1)

The method of claim 1, wherein the sustained decline in eGFR is ≥50%.

### Claim 3 (depends on 1)

The method of claim 1, wherein the end-stage kidney disease (ESKD) comprises sustained eGFR <15 mL/min/1.73 m2, initiation of chronic dialysis treatment and/or renal transplant.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 5)

The method of claim 5, wherein the angiotensin-converting enzyme inhibitor (ACEi) is chosen from captopril, enalapril, and lisinopril.

### Claim 7 (depends on 5)

The method of claim 5, wherein the angiotensin receptor blocker (ARB) is chosen from valsartan, losartan, and irbesartan.

### Claim 8

A method for treating a patient with chronic kidney disease at risk of progression, the method comprising:
administering dapagliflozin once daily to the patient at a dose and duration sufficient to reduce a risk of an incidence of a composite endpoint;
wherein the patient does not have type II diabetes;
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; and
wherein the duration is at least four months.

### Claim 9 (depends on 8)

The method of claim 8, wherein the end-stage kidney disease (ESKD) comprises sustained eGFR <15 mL/min/1.73 m2, initiation of chronic dialysis treatment and/or renal transplant.

### Claim 10 (depends on 8)

The method of claim 8, 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.

### Claim 11 (depends on 8)

The method of claim 8, 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.

### Claim 12 (depends on 11)

The method of claim 11, wherein the angiotensin-converting enzyme inhibitor (ACEi) is chosen from captopril, enalapril, and lisinopril.

### Claim 13 (depends on 11)

The method of claim 11, wherein the angiotensin receptor blocker (ARB) is chosen from valsartan, losartan, and irbesartan.

### Claim 14 (depends on 8)

The method of claim 8, 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 an administration regimen where 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 an administration regimen where 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 an administration regimen where 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 an administration regimen where the patient receives no dapagliflozin;
e) the method numerically reduces the absolute risk of the composite endpoint relative to an administration regimen where the patient receives no dapagliflozin;
f) the method results in a nominally significant risk reduction of the composite endpoint relative to an administration regimen where the patient receives no dapagliflozin;
g) the method results in a numerical reduction in the composite endpoint relative to an administration regimen where 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 an administration regimen where the patient receives no dapagliflozin; and/or
i) the method results in a hazard ratio for time to death from all causes of approximately 0.69 relative to an administration regimen where the patient receives no dapagliflozin.

### Claim 15 (depends on 1)

The method of claim 1, wherein the method further comprises administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of AZD9977 or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 15)

The method of claim 15, wherein the patient is at high risk for hyperkalemia.

### Claim 17 (depends on 15)

The method of claim 15, wherein the therapeutically effective amount of AZD9977 or a pharmaceutically acceptable salt thereof is 15-150 mg daily.

### Claim 18 (depends on 15)

The method of claim 15, wherein the therapeutically effective amount of dapagliflozin is 10 mg orally once per day.

### Claim 19 (depends on 8)

The method of claim 8, wherein the method further comprises administering to the patient a pharmaceutical composition comprising a therapeutically effective amount of AZD9977 or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 19)

The method of claim 19, wherein the patient is at high risk for hyperkalemia.

### Claim 21 (depends on 19)

The method of claim 19, wherein the therapeutically effective amount of AZD9977 or a pharmaceutically acceptable salt thereof is 15-150 mg daily.

### Claim 22 (depends on 19)

The method of claim 19, wherein the amount of dapagliflozin is 10 mg orally once per day.

### Claim 23 (depends on 1)

The method of claim 1, wherein the patient is not on chronic dialysis.

### Claim 24 (depends on 8)

The method of claim 8, wherein the patient is not on chronic dialysis.