FORXIGA (dapagliflozin) APPROVED IN GREAT BRITAIN FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE

FORXIGA (dapagliflozin) APPROVED IN GREAT BRITAIN FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE

·         This approval marks a significant advancement in the treatment of chronic kidney disease for people with and without diabetes, becoming the first new treatment indicated for adults with CKD in nearly 20 years.

• The decision is based on the data from the DAPA-CKD clinical trial. This trial demonstrated that dapagliflozin, in addition to standard care, was the first medicine to show a significant reduction in all-cause mortality in a renal outcomes trial in patients with chronic kidney disease with and without type-2 diabetes.[i]
• There are an estimated 3.5 million people in Great Britain with chronic kidney disease (CKD), [ii] and it is expected to become the fifth leading cause of mortality globally by 2040.[iii]

Luton, UK, 09 August, 2021 – AstraZeneca today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted a licence extension for Forxiga (dapagliflozin) in Great Britain, for the treatment of chronic kidney disease (CKD) in adult patients.[iv]

This decision is based on positive results from the DAPA-CKD Phase III trial, which demonstrated that dapagliflozin, in addition to standard care, was the first medicine to show a significant reduction in all-cause mortality in a renal outcomes trial in patients with chronic kidney disease with and without type-2 diabetes.¹

Professor David Wheeler, Professor of Kidney Medicine at University College London, said “This decision is a significant milestone for people living with chronic kidney disease. It provides healthcare professionals with an effective new option that can slow progression of disease and possibly delay the need for dialysis. As a clinician, I am thrilled to see advances like this, which have the potential to transform the experiences of many of the people living with this condition.”

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.[v] Currently, an estimated 3.5 million people in Great Britain have CKD and it is estimated up to 1.2 million of these people are living with the condition undiagnosed.² This is particularly relevant in Black, Asian and minority ethnic communities, as they are five times more likely to develop CKD that other groups.[vi]

The DAPA-CKD trial demonstrated that dapagliflozin, in addition to standard-of-care treatment, which included an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, reduced the relative risk of worsening of renal function, onset of ESKD, or risk of CV or renal death by 39% (ARR=5.3%, HR=0.61, 95% CI: 0.51 to 0.72, p<0.001), the primary composite endpoint, compared to placebo in patients with CKD Stages 2-4 and elevated urinary albumin excretion (albumin-to-creatine ratio of 22.6 to 565 mg/mmol). Dapagliflozin also significantly reduced the relative risk of the secondary outcome of death from any cause by 31% (ARR=2.1%, HR=0.69; 95% CI: 0.53 to 0.88, p=0.004) compared to placebo.¹

Tom Keith-Roach, President, AstraZeneca UK: “Today’s approval of dapagliflozin marks a significant advancement in the treatment of chronic kidney disease for people with and without diabetes, becoming the first new treatment indicated for adults with CKD in nearly 20 years. Dapagliflozin demonstrated significant reductions in progression to end stage renal disease, hospitalisations, and death in CKD, and has the potential to make a difference to the lives of many of the people living with this condition. There is now an urgent need to work with the clinical community to diagnose CKD earlier and to ensure patients have access to a medicine that prevents disease progression and premature death.”

The safety and tolerability of dapagliflozin in CKD was consistent with the well-established safety profile of the medicine. In the trial, 633 (29.5%) and 729 (33.9%) patients treated with dapagliflozin and placebo respectively experienced a serious adverse event.

There were 118 (5.5%) and 123 (5.7%) patients in the dapagliflozin and placebo arm respectively who discontinued treatment due to an AE. 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.¹ The were 127 (5.9%) and 90 (4.2%) patients in the dapagliflozin and placebo arms respectively who reported symptoms of volume depletion.¹

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

[ii] AstraZeneca Data on File. REF-113657. July 2021.

[iii] Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018; 392:2052–2090.

[iv] 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 July 2021.

[v] NHS. Chronic kidney disease. Available at: https://www.nhs.uk/conditions/kidney-disease/ Last accessed July 2021.

[vi] Kidney Care UK. Facts and Stats. Available at: https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/ Last accessed: July 2021.