AstraZeneca presents data at ASN Kidney Week 2022 reinforcing urgent need for early screening of chronic kidney disease and the benefits of earlier treatment initiation for patients and healthcare systems

REVEAL-CKD data show alarming prevalence of undiagnosed Stage 3 chronic kidney disease across France, Germany, Italy, Japan and US

Findings from INSIDE-CKD demonstrate that FARXIGA can cut 33 percent of healthcare costs by delaying disease progression and reducing incidence of cardiorenal events

AstraZeneca, a leader in cardiorenal research, presented new data at the American Society of Nephrology (ASN) Kidney Week 2022 in Orlando, Florida, US on the importance of earlier screening and diagnosis of chronic kidney disease (CKD) and the impact of FARXIGA® (dapagliflozin) on reducing healthcare costs.1,2 These findings were also simultaneously published in the Journal of the American Society of Nephrology.

CKD affects 850 million people worldwide with increasing prevalence,3 yet the vast majority of patients go undiagnosed.4 Data from the REVEAL-CKD multinational study found high rates of underdiagnosis, 61.6% to 95.5%, in the countries studied (US, Italy, Germany, Japan and France). Country-specific electronic medical records and insurance claims were analyzed for patients with estimated glomerular filtration rate (eGFR) between ≥30 and <60 mL/min/1.73 m2, equal to CKD Stage 3, who lacked a diagnosis of CKD. This analysis further demonstrated that once a diagnosis was made, patients did receive timely CKD monitoring and management of their disease, leading to real-life patient benefits.1

The importance of receiving a CKD diagnosis can be seen in its impact on annual kidney function decline, i.e., the eGFR slope. The REVEAL-CKD trial evaluated eGFR decline before and after CKD diagnosis was recorded for 27,000 patients in the US TriNetX database. These patients had a median eGFR decline in the two-year period prior to CKD diagnosis of -4.12 (95% confidence interval [CI]: -4.23, -4.02) and in the two-year period after diagnosis of only -0.30 (95% CI: -0.44, -0.14).5  

Dr. Navdeep Tangri, Professor of Medicine at University of Manitoba Department of Internal Medicine, Winnipeg, Manitoba, Canada said: “The level of underdiagnosis of chronic kidney disease, even in countries with well-established and-financed healthcare systems, is alarming. These data from REVEAL-CKD reinforce the need to proactively screen and diagnose early-stage kidney disease so that patients can receive guideline-directed monitoring and treatment. This can prevent or delay progression to kidney failure and other serious comorbidities.”

In addition to the patient need, there are significant healthcare costs associated with CKD, especially as it progresses to kidney failure and cardiorenal events. INSIDE-CKD estimated the direct medical care cost-offsets of a reduced incidence of clinical events, showing that FARXIGA significantly reduces healthcare resource utilization by delaying CKD progression and reducing incidence of cardiorenal events. Across 23 countries and 100,000 patients, there was a 33% cost reduction when patients were treated with FARXIGA in addition to standard of care, compared to standard of care alone, resulting in savings of $205M USD over a 3-year period.2

Another analysis of DAPA-CKD data presented at ASN furthermore found that FARXIGA treatment reduced the rate of all-cause hospital admissions among patients with CKD, with or without type 2 diabetes (T2D).6 These findings demonstrate implications not only for patient quality of life, but also on the overall healthcare burden and expenditure attributed to CKD care.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Chronic kidney disease is a silent, progressive killer that remains underdiagnosed. These data presented at ASN Kidney Week 2022 not only provide a comprehensive view of the costs associated with chronic kidney disease and the toll it takes on patient lives, but also how FARXIGA can cut this significant burden with reduced rates of all-cause hospital admissions and healthcare resource utilization. If clinical treatment guidelines were fully implemented, highlighting the need for preventive treatment strategies, patients’ risk of adverse kidney, mortality and cardiovascular outcomes can be ameliorated.”    

In addition to presenting data at ASN Kidney Week 2022 on the urgent need for earlier diagnosis and screening, AstraZeneca supported the International Society of Nephrology in creating this quick one-minute quiz to offer insight into whether a patient may be at risk for CKD and to provide them with more information on the risk factors to be aware of to help start the conversation with their doctor.

INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)

FARXIGA is indicated:

  • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular (CV) disease or multiple CV risk factors
  • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
  • to reduce the risk of sustained eGFR decline, endstage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression

FARXIGA is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

FARXIGA is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting based upon its mechanism of action.

FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations.

DOSING

To improve glycemic control, the recommended starting dose is 5 mg orally once daily. Dose can be increased to 10 mg orally once daily for additional glycemic control.

For all other indications, the recommended dose is 10 mg orally once daily.

IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5 mg and 10 mg tablets

Contraindications

  • Prior serious hypersensitivity reaction to FARXIGA
  • Patients on dialysis

Warnings and Precautions

  • Ketoacidosis in Diabetes Mellitus has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
  • Volume Depletion: FARXIGA can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function
  • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
  • Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
  • Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare but serious, life-threatening cases have been reported in patients with diabetes mellitus receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA
  • Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately

Adverse Reactions

In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters

  • Lactation: FARXIGA is not recommended when breastfeeding

Please see link to US Full Prescribing Information for FARXIGA.

Notes

CKD
CKD is a serious, progressive condition defined by decreased kidney function (shown by reduced eGFR or markers of kidney damage, or both, for at least three months).4 The most common causes of CKD are diabetes, hypertension and glomerulonephritis.7 CKD is associated with significant patient morbidity and an increased risk of cardiovascular (CV) events, such as heart failure (HF) and premature death.8 In its most severe form, known as kidney failure, kidney damage and deterioration of kidney function have progressed to the point where dialysis or kidney transplantation are required.8 The majority of patients with CKD will die from CV causes before reaching kidney failure.9

DAPA-CKD
DAPA-CKD was an international, multi-center, randomized, double-blinded Phase III trial in 4,304 patients designed to evaluate the efficacy of FARXIGA 10mg, compared with placebo, in patients with CKD Stage 2-4 and elevated urinary albumin excretion, with and without T2D. FARXIGA was given once daily in addition to standard of care. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of kidney failure or death from CV or renal cause). The secondary endpoints included the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, kidney or renal death), the composite of CV death or hospitalization for HF (hHF), and death from any cause. The trial was conducted in 21 countries. Detailed results from the trial were published in The New England Journal of Medicine.10

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

About AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

  1. Tangri N, et al. REVEAL-CKD: Management and Monitoring of Patients with CKD Stage 3 in France, Germany, Italy, Japan, and the USA. Presented at: American Society of Nephrology (ASN) Kidney Week 2022, 3-6 November 2022, Orlando, Florida, USA.
  2. McEwan, et al. Translating the Findings of DAPA-CKD to Reductions in Healthcare Resource Utilization from a Global Perspective. Presented at: American Society of Nephrology (ASN) Kidney Week 2022, 3-6 November 2022, Orlando, Florida, USA.
  3. Jager KJ, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803-1805.
  4. Bikbov B, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-733.
  5. Tangri N, et al. REVEAL CKD: Estimated Glomerular Filtration Rate (eGFR) Decline Before and After a CKD Diagnosis Among Patients with CKD Stage 3. Presented at: American Society of Nephrology (ASN) Kidney Week 2022, 3-6 November 2022, Orlando, Florida, USA.
  6. Schechter M, et al. Dapagliflozin effect on hospital admissions in patients with chronic kidney disease: A post hoc analysis of the DAPA-CKD trial. Presented at: American Society of Nephrology (ASN) Kidney Week 2022, 3-6 November 2022, Orlando, Florida, USA.
  7. National Kidney Foundation [Internet]. Kidney Disease: Causes; 2015 [cited 2022 Nov 05]. Available from: https://www.kidney.org/atoz/content/kidneydiscauses.
  8. Centers for Disease Control and Prevention (CDC) [Internet]. Chronic kidney disease in the United States; 2019 [cited 2022 Oct 11]. Available from: https://www.cdc.gov/kidneydisease/publications-resources/2019-national-facts.html.
  9. Briasoulis A, et al. Chronic kidney disease as a coronary artery disease risk equivalent. Curr Cardiol Rep. 2013;15(3):340.
  10. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.