NICE ISSUES FINAL RECOMMENDATION FOR FORXIGA (dapagliflozin) IN THE TREATMENT OF ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE

NICE ISSUES FINAL RECOMMENDATION FOR FORXIGA (dapagliflozin) IN THE TREATMENT OF ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE

• Today’s decision will give eligible patients access to the first treatment option indicated for chronic kidney disease (CKD) in nearly 20 years.
• It is estimated that one in 10 people are affected by CKD in the UK, resulting in an estimated 40,000–45,000 premature deaths every year.^[1],[2]
• Following ongoing collaboration and review of clinical data, NICE has recommended removing the urine albumin-to-creatinine ratio (uACR) testing restriction in the type 2 diabetes (T2D) population, issued as part of their draft recommendation in November 2021, facilitating access to an increased number of patients.^[3]
• AstraZeneca estimates that approximately 373,000 adults living with CKD in England, Wales and Northern Ireland could be eligible for treatment under this recommendation.^[4]

Luton, UK, Thursday 3 February 2022 – AstraZeneca today announced that the National Institute for Health and Care Excellence (NICE) has issued a Final Appraisal Document (FAD) recommending Forxiga (dapagliflozin) within its marketing authorisation for the treatment of adults with chronic kidney disease (CKD).³

Dapagliflozin is recommended as an option for treating chronic kidney disease (CKD) in adults. It is recommended only if:

• it is an add-on to optimised standard care including the highest tolerated licensed dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), unless these are contraindicated, and
• people have an estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m² to 75 ml/min/1.73 m² at the start of treatment and:
• have type 2 diabetes or
• have a urine albumin-to-creatinine ratio (uACR) of 22.6 mg/mmol or more.³

The NICE appraisal committee recognises that uACR testing is not currently implemented consistently across the NHS,³ and following further review of the clinical data, has determined that there is enough evidence to support the removal of the uACR testing restriction in patients with T2D.³ This restriction was originally issued as part of the NICE draft recommendation in November 2021 and its removal will facilitate access to an increased number of patients who are eligible.^4,[5] Based on current uACR testing rates, AstraZeneca estimates that approximately 373,000 adults living with CKD in England, Wales and Northern Ireland could be eligible for treatment under this updated recommendation. Should uACR testing be consistently implemented across all patient populations, it is estimated that a further 66,000 could be eligible.⁴

Professor James Burton, Professor of Renal Medicine and Honorary Consultant Nephrologist, University of Leicester, said: “I am thrilled by this decision from NICE, as this expanded recommendation is going to have a genuine impact on the way that kidney doctors and GPs can treat their patients. For the first time in almost two decades, eligible people living with chronic kidney disease will have access to a new treatment option that has been shown to slow kidney decline and potentially delay transplant or dialysis. Given the impact those treatments can have on the quality of life of patients and those around them, this represents a significant milestone for many people living with kidney disease.”

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] It is estimated that one in 10 people are affected by CKD in the UK,¹ resulting in an estimated 40,000–45,000 premature deaths every year,² and around 1 million people in England may be living with the condition undiagnosed.^[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,² 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 1.3% of NHS spending overall.^[9]

This recommendation is an important step forward in the management of CKD and addresses a significant unmet need. 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. The trial showed that dapagliflozin reduced the risk of a primary composite outcome of: a sustained decline in eGFR of at least 50%, progression to end-stage kidney disease (ESKD), or death from renal or CV causes when compared to placebo ([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 final recommendation from NICE is a watershed moment for people living with CKD, providing access to a new treatment option, which has the potential to change the way CKD is managed. We will work closely with NICE and the NHS to pull this through into clinical practice, supporting earlier identification of CKD to prevent disease progression and potentially defer the need for life-altering treatments like dialysis.”

The safety and tolerability of dapagliflozin in patients with CKD was consistent with the well-established 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] Kidney Care UK. Chronic kidney disease (CKD). Available at: https://www.kidneycareuk.org/about-kidney-health/conditions/ckd/ Last accessed February 2022.

[2] 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 February 2022.

[3] National Institute for Health and Care Excellence. Dapagliflozin for treating chronic kidney disease: Final appraisal document – Published 3 February 2022.

[4] AstraZeneca Data on File. REF- 138227. February 2022.

[5] National Institute for Health and Care Excellence. Dapagliflozin for treating chronic kidney disease: Appraisal Consultation Document – Published 5 November 2021.

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

[7] NHS England. Chronic Kidney Disease in England: The Human and Financial Cost. Available at: https://www.england.nhs.uk/improvement-hub/wp-content/uploads/sites/44/2017/11/Chronic-Kidney-Disease-in-England-The-Human-and-Financial-Cost.pdf Last accessed February 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 February 2022.

[9] Kerr M, Bray B, Medcalf J, et al. Estimating the financial cost of chronic kidney disease to the NHS

in England. Nephrol Dial Transplant. 2012;27(Supple 3):iii73-iii80.

[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 February 2022.