NICE recommends AstraZeneca drug for adult chronic kidney disease  

The National Institute for Health and Care Excellence (NICE) in the UK has issued a Final Appraisal Document (FAD) recommending AstraZeneca’s Forxiga (dapagliflozin) within its marketing authorisation for the treatment of adults with chronic kidney disease (CKD).¹ 

Conditions 

Dapagliflozin is recommended as an option for treating 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.¹

Background 

The NICE appraisal committee recognised 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.¹ 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.^2,3  

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.² 

Context 

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).² 

The trial  

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.⁴ 

Official comments 

Professor James Burton, Professor of Renal Medicine and Honorary Consultant Nephrologist at the 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.” 

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.” 

References 

1. Kidney Care UK. Chronic kidney disease (CKD). Available at: https://www.kidneycareuk.org/about-kidney-health/conditions/ckd/ Last accessed February 2022.
2. AstraZeneca Data on File. REF- 138227. February 2022.
3. National Institute for Health and Care Excellence. Dapagliflozin for treating chronic kidney disease: Appraisal Consultation Document – Published 5 November 2021.
4. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-1446.