The National Institute for Health and Care Excellence (NICE) has issued an Appraisal Consultation Document (ACD) for AstraZeneca’s Forxiga (Dapagliflozin) within its marketing authorization for the treatment of adults with chronic kidney disease (CKD).
This decision follows the recent license extension granted for Dapagliflozin in August by the Medicines and Healthcare products Regulatory Agency (MHRA), and is based on positive results from the DAPA-CKD Phase III trial.
NICE proposes to recommend, Dapagliflozin as an option for treating CKD in adults, only if:
- it is an add-on to optimized standard care including angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), unless these are contraindicated or not tolerated, and
- people have an estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m2 to 75 ml/min/1.73 m2and:
- a urine albumin-to-creatinine ratio (uACR) of 22.6 mg/mmol or more or
a uACR of 3 mg/mmol or more and type 2 diabetes (T2D).
- a urine albumin-to-creatinine ratio (uACR) of 22.6 mg/mmol or more or
People living with CKD have had few treatment innovations in the last 20 years and this recommendation marks a significant advancement in the management of the condition. However, in order for patients to access Dapagliflozin under this recommendation, they must have a uACR diagnostic test. The NICE appraisal committee recognise that uACR testing is not implemented consistently across the NHS. AstraZeneca is continuing to engage with NICE to discuss enabling access for all patients within Dapagliflozin’s licenced indication who could clinically benefit and the implications to patient access if the recommendation remains limited to subgroups based on uACR levels.
Professor James Burton, Professor of Renal Medicine and Honorary Consultant Nephrologist, University of Leicester, said: “This is welcome news for people living with chronic kidney disease, providing them with access to a new and long-awaited treatment option for a disease that affects millions. This announcement represents an important milestone that could make a difference to the lives of many people living with the condition ,and even delay their need for dialysis.”
Tom Keith-Roach, President, AstraZeneca UK: “Today’s draft recommendation from NICE is a step in the right direction but we have more work to do to ensure broad and equitable access to Dapagliflozin, particularly for CKD patients without diabetes. CKD affects around one in 10 people in the UK and has seen very little progress in treatment options for nearly 20 years… We are working with NICE through the appraisal process towards a final appraisal determination that enables access for all CKD patients who would be clinically appropriate and may benefit.”
Dapagliflozin was previously used as:
Dapagliflozin is used along with diet and exercise to improve glycemic control in adults with type 2 diabetes and to reduce the risk of hospitalization for heart failure among adults with type 2 diabetes and known cardiovascular disease or other risk factors. It appears more useful than empagliflozin.
In addition, dapagliflozin is indicated for the treatment of adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure. It is also indicated to reduce the risk of kidney function decline, kidney failure, cardiovascular death and hospitalization for heart failure in adults with chronic kidney disease who are at risk of disease progression.
In the European Union it is indicated in adults:
- for the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise:
- as monotherapy when metformin is considered inappropriate due to intolerance;
- in addition to other medicinal products for the treatment of type 2 diabetes;
- for the treatment of insufficiently controlled type 1 diabetes mellitus as an adjunct to insulin in patients with BMI ≥ 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy; and
- for the treatment of heart failure with reduced ejection fraction
What is chronic kidney disease (CKD)?
Chronic kidney disease includes conditions that damage your kidneys and decrease their ability to keep you healthy by doing the jobs listed. If kidney disease gets worse, wastes can build to high levels in your blood and make you feel sick. You may develop complications like high blood pressure, anemia (low blood count), weak bones, poor nutritional health and nerve damage. Also, kidney disease increases your risk of having heart and blood vessel disease. These problems may happen slowly over a long period of time. Chronic kidney disease may be caused by diabetes, high blood pressure and other disorders. Early detection and treatment can often keep chronic kidney disease from getting worse. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life.
What causes CKD?
The two main causes of chronic kidney disease are diabetes and high blood pressure, which are responsible for up to two-thirds of the cases. Diabetes happens when your blood sugar is too high, causing damage to many organs in your body, including the kidneys and heart, as well as blood vessels, nerves and eyes. High blood pressure, or hypertension, occurs when the pressure of your blood against the walls of your blood vessels increases. If uncontrolled, or poorly controlled, high blood pressure can be a leading cause of heart attacks, strokes and chronic kidney disease. Also, chronic kidney disease can cause high blood pressure.
Other conditions that affect the kidneys are:
- Glomerulonephritis, a group of diseases that cause inflammation and damage to the kidney’s filtering units. These disorders are the third most common type of kidney disease.
- Inherited diseases, such as polycystic kidney disease, which causes large cysts to form in the kidneys and damage the surrounding tissue.
- Malformations that occur as a baby develops in its mother’s womb. For example, a narrowing may occur that prevents normal outflow of urine and causes urine to flow back up to the kidney. This causes infections and may damage the kidneys.
- Lupus and other diseases that affect the body’s immune system.
- Obstructions caused by problems like kidney stones, tumors or an enlarged prostate gland in men.
- Repeated urinary infections.
What are the symptoms of CKD?
Most people may not have any severe symptoms until their kidney disease is advanced. However, you may notice that you:
- feel more tired and have less energy
- have trouble concentrating
- have a poor appetite
- have trouble sleeping
- have muscle cramping at night
- have swollen feet and ankles
- have puffiness around your eyes, especially in the morning
- have dry, itchy skin
- need to urinate more often, especially at night.
Anyone can get chronic kidney disease at any age. However, some people are more likely than others to develop kidney disease. You may have an increased risk for kidney disease if you:
- have diabetes
- have high blood pressure
- have a family history of kidney failure
- are older
- belong to a population group that has a high rate of diabetes or high blood pressure, such as African Americans, Hispanic Americans, Asian, Pacific Islanders, and American Indians.
Prevalence of Chronic kidney disease:
It is estimated that a current 1.8 million people in England have diagnosed CKD, and it is expected to become the fifth leading cause of mortality globally by 2040. AstraZeneca estimates that approximately 91,000 adults living with CKD in England could be eligible for treatment under the current recommendation.
The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health in England, which publishes guidelines in four areas:
- the use of health technologies within the National Health Service (England) and within NHS Wales (such as the use of new and existing medicines, treatments and procedures)
- clinical practice (guidance on the appropriate treatment and care of people with specific diseases and conditions)
- guidance for public sector workers on health promotion and ill-health avoidance
- guidance for social care services and users.
These appraisals are based primarily on evidence-based evaluations of efficacy, safety and cost-effectiveness in various circumstances.
AstraZeneca plc is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas including oncology, cardiovascular, gastrointestinal, infection, neuroscience, respiratory, and inflammation. It has been involved in developing the Oxford-AstraZeneca COVID-19 vaccine.
The company was founded in 1999 through the merger of the Swedish Astra AB and the British Zeneca Group (itself formed by the demerger of the pharmaceutical operations of Imperial Chemical Industries in 1993). Since the merger it has been among the world’s largest pharmaceutical companies and has made numerous corporate acquisitions, including Cambridge Antibody Technology (in 2006), MedImmune (in 2007), Spirogen (in 2013) and Definiens (by MedImmune in 2014). It has its research and development concentrated in three strategic centres: Cambridge, England; Gothenburg, Sweden and Gaithersburg in Maryland, U.S.