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Heavyweight! Significant benefit of engramine for CKD, phase III EMPA-KIDNEY trial meets endpoints
Time : 2022-05-12
Chronic kidney disease (CKD) has become a global public health problem, with approximately 5-10 million people dying from CKD each year worldwide, and there is a long-standing need for new therapeutic options, as there are only a limited number of drugs proven in clinical studies to improve the clinical prognosis of CKD, other than controlling risk factors such as hypertension and diabetes.

On 16 March 2022, the official website of the EMPA-KIDNEY trial published a news release stating that the Independent Data Monitoring Committee recommended that the study could be closed early due to the significant efficacy benefit in the study's engramine group, which met the primary endpoint. It is reported that the EMPA-KIDNEY randomised controlled trial is the largest clinical trial to date of a sodium glucose cotransporter 2 (SGLT-2) inhibitor for the treatment of CKD, assessing the efficacy and safety of engramine in preventing the progression of CKD and cardiovascular death .


The EMPA-KIDNEY study is a large randomised, double-blind, placebo-controlled trial that included a wider range of patients with CKD, with inclusion criteria including

Adult patients.

Estimated glomerular filtration rate (eGFR) ≥20 to <45 ml/min/1.73 m² or eGFR ≥45 ml/min/1.73 m² and urinary albumin/creatinine ratio (UACR) ≥200 mg/g (or UACR ≥300 mg/g).

The investigator determines that the patient is amenable to a sodium SGLT-2 inhibitor.

A renin-angiotensin system inhibitor (RASi) may be used.

Patients in the engramine group received 10mg engramine daily and the control group received placebo.

Primary composite endpoints include.

Progression of renal disease (end-stage renal disease, sustained decline in eGFR to <10 ml/min/1.73 m², renal death or sustained decline in eGFR of ≥40% after randomisation grouping).

Key secondary endpoints included: hospitalization for heart failure or cardiovascular death; all-cause hospitalization; all-cause death .

EMPA-KIDNEY trial subject information

A total of 6609 patients with CKD were enrolled in the EMPA-KIDNEY trial, with a mean age of 64 (SD=14) years and 67% were male. The subjects were from 8 regions and countries in Europe, America and Asia, including China. Regarding the etiology, 31% of the patients had diabetic nephropathy, 25% had glomerulonephropathy, 22% had hypertension or ischaemic nephropathy, 12% had other nephropathy and 10% had unknown etiology.

At baseline all patients had an eGFR ≥20 ml/min/㎡, with a mean eGFR of 37.5 (SD=15) ml/min/㎡, 78% of patients had an eGFR <45 ml/min/㎡ and 34% had an eGFR <30 ml/min/㎡.

For urinary protein, the mean UACR was 412 (IQR=94-1190) mg/g, 20% of patients had no proteinuria and 48% had a UACR <300 mg/g.

In terms of co-morbidities, 46% of patients had diabetes and 27% had cardiovascular disease.

Overall, the EMPA-KIDNEY study was the largest clinical trial of patients with CKD and a larger proportion of patients with CKD without diabetes.

The range of indications for SGLT-2 inhibitors is expanding

SGLT-2 inhibitors are a new class of glucose-lowering drugs, including engramine, dagliflozin, kagliflozin and eltogliptin. In recent years, the range of indications for SGLT-2 inhibitors has been expanding as the renal and cardiac benefits of SGLT-2 inhibitors have been demonstrated with the publication of results from large randomised clinical trials.

In 2019, the CREDENCE study results were published, and the administration of cabergoline to patients with type 2 diabetes combined with CKD significantly reduced the risk of the primary endpoint (renal composite endpoint and cardiovascular death) by up to 30% and did not increase the risk of fracture, making it the first glucose-lowering agent with a renal hard endpoint benefit .

In 2020, the DAPA-CKD study showed that dagliflozin reduced the incidence of the cardio-renal composite endpoint in patients with CKD, regardless of whether they had diabetes. 2021, dagliflozin was approved for the treatment of CKD in the US and EU.

The cardio-renal benefit of engramine treatment has been demonstrated in several studies, long before the EMPA-KIDNEY study.

The EMPEROR-Reduced trial included 3730 patients with heart failure and showed that engramine reduced the incidence of the primary composite endpoint of cardiovascular death or hospitalisation for heart failure in patients with reduced ejection fraction heart failure. The secondary endpoint, with or without the EMPA-REG OUTCOME study, demonstrated a 39% reduction in the risk of new and worsening nephropathy compared to placebo in adults with type 2 diabetes combined with cardiovascular disease.

In March 2020, the FDA granted fast track to a clinical study of engramine to reduce the risk of kidney disease progression and cardiovascular death in adults with CKD .

The results of the EMPA-KIDNEY study are reported to be released to the public within this year. According to the Independent Data Monitoring Committee's plans, detailed trial results will include data on whether engramine is beneficial for specific patient groups, as well as safety data. We will keep you updated with the results of the study on MediPulse Kidney Disease.

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