FORXIGA (DAPAGLIFLOZIN) ACCEPTED FOR USE IN SCOTLAND FOR THE TREATMENT OF ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE

• Scottish Medicines Consortium (SMC) issues positive recommendation for dapagliflozin for the treatment of chronic kidney disease (CKD) in adults.^[1]
• Today’s decision will give eligible patients in Scotland access to the first new additional treatment option indicated for CKD in nearly 20 years.
• Kidney disease is common in Scotland, with around 3.2% of the population living with CKD.^[2] AstraZeneca estimates that approximately, up to 53,000 adults living with CKD in Scotland could be eligible for treatment under this recommendation.^[3]

London, UK, Monday 9 May 2022 – AstraZeneca today announced that Forxiga (dapagliflozin) has been accepted for restricted use within NHS Scotland by the Scottish Medicines Consortium (SMC) for the treatment of adults with chronic kidney disease (CKD).¹

Dapagliflozin is recommended in patients with an estimated glomerular filtration rate (eGFR) of ≥25 to ≤75 ml/min/1.73m² at treatment initiation, who are receiving an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) (unless these are not tolerated or contraindicated) and have a urine albumin-creatinine ratio (uACR) of at least 23 mg/mmol and/or type 2 diabetes (T2D).¹

This decision is in line with the National Institute for Health and Care Excellence (NICE) recommendation from February 2022 for dapagliflozin within the same indication.^[4] The SMC recommendation also does not include a uACR restriction for the T2D patient population.¹ Currently, uACR testing is not implemented consistently across the NHS in the United Kingdom,^[5] and this decision facilitates access for an increased number of patients in Scotland. AstraZeneca estimates that approximately, up to 53,000 adults living with CKD in Scotland could be eligible for treatment under this recommendation.³

Professor Patrick Mark, Professor of Nephrology and Honorary Consultant Nephrologist, Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital Glasgow, said: “For people living with chronic kidney disease in Scotland and the physicians who treat them, today’s announcement will be an extremely welcome milestone. This decision could have a significant impact on patients’ lives, as they will now have access to a much-needed [additional] treatment option that has demonstrated its ability to slow kidney decline, reduce their risk for hospitalisation and delay the need for transplant or dialysis.”

CKD is a long-term condition where the kidneys do not work as well as they should and are unable to remove waste products from the body.^[6] Kidney disease is common in Scotland, with around 3.2% of the population living with CKD.² Across the UK, an estimated 20 people with CKD will progress to end-stage kidney disease (ESKD) every day, resulting in an estimated 40,000–45,000 premature deaths every year.^[7] This is particularly relevant in Black, Asian and minority ethnic communities, as they are not only five times more likely to develop CKD than other groups,⁷ but are also less likely to receive access to treatments such as transplantation.^[8] CKD also represents a significant burden on the UK healthcare system, accounting for £1.45 billion of NHS spending every year.^[9]

Dr. Kevin Fernando, GP Partner North Berwick Health Centre, GPwSI CVRM, Scottish Lead Primary Care Diabetes Society, said: “The SMC’s decision is great news for people living with CKD in Scotland, who have waited many years to see improvements in treatment in this disease setting. It will also mark a much-needed treatment shift for the management of chronic kidney disease in primary care, particularly in people living with this condition who also have type 2 diabetes. I am pleased to see the SMC is making positive steps to bring practice in line with the latest research, enabling eligible patients to access a new and effective treatment option.”

The recommendation is based on results from the DAPA-CKD Phase III trial, which demonstrated that dapagliflozin, in addition to standard care, was more effective than placebo plus standard of care in adults with or without type 2 diabetes, who had an eGFR of 25 to 75 ml/min/1.73 m² and a uACR of 22.6–565 mg/mmol, in reducing the risk of a primary composite outcome of: a sustained decline in eGFR of at least 50%, progression to ESKD, or death from renal or CV causes ([9.2% vs 14.5% patients with event, respectively]) (hazard ratio [HR] = 0.61 [95% confidence interval {CI} 0.51-0.72; p<0.001).^[10]

Tom Keith-Roach, President, AstraZeneca UK: “This is an incredibly important decision for adults living with CKD in Scotland.  Dapagliflozin is the first new treatment option for these patients in almost 20 years with the potential to transform CKD management, particularly in primary care to prevent progression and hospitalisation, reduce CV risk, and defer the need for life-changing treatments like dialysis and transplantation.  We will work with NHS Scotland to pull this recommendation through into routine practice making this new treatment available to patients as soon as possible.”

The overall safety and tolerability of dapagliflozin in patients with CKD was consistent with the known safety profile of the medicine.^[11] The rates of adverse events of special interest including: renal AEs (7.2% vs. 8.7%); definite or probable diabetic ketoacidosis (0% vs <0.1%); major hypoglycaemic events (0.7% vs. 1.3%); amputations (1.6% vs. 1.8%) and fractures (4.0% vs 3.2%) were generally low and balanced across the dapagliflozin and placebo arm respectively. The were 127 (5.9%) and 90 (4.2%) patients in the dapagliflozin and placebo arms respectively who reported symptoms of volume depletion.¹⁰

[1] Scottish Medicines Consortium (SMC). Dapagliflozin for the treatment of adult patients with chronic kidney disease: Decision Advice Document (DAD) – Published 9 May 2022.

[2] Kidney Research UK. Pioneering kidney research in Scotland. Available at: https://kidneyresearchuk.org/wp-content/uploads/2019/02/Scottish_Supplement_WEB_20161121.pdf Last accessed May 2022.

[3] AstraZeneca Data on File, REF-148076. May 2022.

[4] ©NICE [2022] Dapagliflozin for treating chronic kidney disease: Technology Appraisal Guidance. Available at: https://www.nice.org.uk/guidance/ta775 Last accessed May 2022.

[5] Healthcare Quality Improvement Partnership. National Chronic Kidney Disease Audit: National Report (Part 1). Available at: https://www.hqip.org.uk/wp-content/uploads/2018/02/HtoEm0.pdf Last accessed May 2022.

[6] NHS. Chronic Kidney Disease. Available at: https://www.nhs.uk/conditions/kidney-disease/ Last accessed May 2022.

[7] Kidney Care UK. Facts and stats. Available at: https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/#:~:text=There%20are%2040%2D45%2C000%20premature,UK%20will%20develop%20kidney%20failure Last accessed May 2022.

[8] Kidney Research UK. Kidney health inequalities in the UK. Available at: https://kidneyresearchuk.org/wp-content/uploads/2019/09/Health_Inequalities_lay_report_FINAL_WEB_20190311.pdf Last accessed May 2022.

[9] Think Kidneys UK. Transforming participation in chronic kidney disease. Available at: https://www.thinkkidneys.nhs.uk/ckd/wp-content/uploads/sites/4/2019/01/Transforming-Participation-in-Chronic-Kidney-Disease-1.pdf Last accessed May 2022.

[10] Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-1446.

[11] Electronic Medicines Compendium. Forxiga 10 mg film-coated tablets. Last updated August 2021. Available at: https://www.medicines.org.uk/emc/product/7607/smpc#gref Last accessed May 2022.