Boringer Ingelheim and Lilly (Eli Lilly) recently released positive results for the EMPA-KIDNEY 3 clinical trial (NCT03594110) at the American Society of Nephrology Kidney Week (ASN Kedney Week) 2022. The data showed that the trial reached the primary end point: treatment with the SGLT2 inhibitor Jardiance (Chinese trade name, empagliflozin, Englegrizin) had significant renal and cardiovascular benefits in adult patients with chronic kidney disease (CKD). The data have been published simultaneously in the top international medical journal, the New England Journal of Medicine (NEJM), see: Empagliflozin in Patients with Chronic Kidney Disease 。
The EMPA-KIDNEY is a multi-national, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the impact of Jardiance on renal disease progression and cardiovascular mortality. The primary outcome was defined as the time to the first event of cardiovascular death or renal disease progression. Renal disease progression was defined as end-stage renal disease (requiring renal replacement therapy, such as dialysis or kidney transplantation), a sustained decline in eGFR to <10mL/min/1.73m2, renal death, and a sustained 40% decrease in eGFR from randomization. Key secondary outcomes include cardiovascular death or heart failure hospitalizations, all-cause hospitalization, and all-cause death. Patients in the trial were randomized on a current standard of care basis, treated on Jardiance 10mg or placebo.
EMPA-KIDNEY is the largest and most extensive SGLT2 inhibitor trial for CKD, including 6,609 adult CKD patients with a wide cause of disease (with or without diabetes, with or without proteinuria), many of whom had extensive comorbidities such as cardiovascular, renal or metabolic diseases. The trial assessed renal and cardiovascular outcomes in populations with varying CKD severity.
The EMPA-KIDNEY trial provides new evidence for clinically common patients. The results showed that the trial reached the primary endpoint: a median follow-up of 2.0 years, and Jardiance treatment significantly reduced the risk of nephropathy progression or cardiovascular death as compared with placebo; p <0.0001).
CKD progression leads to dialysis or kidney transplantation, and therefore new therapies are urgently needed to delay disease progression in CKD. The results of the EMPA-KIDNEY trial suggest that Jardiance can produce a benefit in adult patients at risk of CKD progression, including those with or without diabetes, as well as with extensive renal function. By reducing the risk of renal disease progression or cardiovascular disease death, Jardiance has the potential to have positive effects on the global healthcare system.
EMPA-KIDNEY was the first SGLT2 inhibitor CKD trial to demonstrate a significant reduction in all-cause hospitalization rates as compared to placebo (14%;HR=0.86;95%CI:0.78-0.95; p=0.0025), one of the key, pre-specified, secondary validation endpoints. CKD doubles a person's risk of hospitalisation and is the leading cause of death worldwide. In the United States, CKD patients for 35% – 55% of total medical costs.
Other key secondary endpoints, reductions in HF hospitalization, cardiovascular death, all-cause deaths were not statistically significant, but the ability to detect this was limited by the number of the events observed. These reductions in risk for end points are consistent with the full evidence from other trials, where these outcomes were statistically significant.
The overall safety data in this trial were largely consistent with previous studies, confirming the good safety of Jardiance.
Professor Richard Haynes, co-chief investigator of the EMPA-KIDNEY trial, said: " The EMPA-KIDNEY trial is designed to include a wider range of patients than ever before. Previous trials of SGLT2 inhibitors have mainly targeted certain CKD populations, such as those with diabetes mellitus or high protein levels in the urine. The results of positive trials performed today in a broad CKD population suggest the opportunity to improve the treatment of this disease and to prevent patients from requiring dialysis.”
Carinne Brouillon, head of medication for the Boehringer Ingelheim, said: " The Boehringer Ingelheim and the Lilly Alliance are very proud that the EMPA-KIDNEY trial provides another critical moment for the Jardiance. Today's data provide substantial evidence for our clinical program, which includes more than 700,000 adult patients with cardiovascular, renal, and metabolic diseases. The EMPA-KIDNEY trial strengthens the potential role of Jardiance in changing the way these interrelated diseases are managed.”
Cardio-kidney-metabolic conditions is the leading cause of death worldwide, causing up to 20 million deaths each year. The EMPOWER Clinical Project, the most extensive and comprehensive of all SGLT2 inhibitors, is exploring the impact of Jardiance on the major clinical cardiovascular and renal outcomes of cardiorerenetabolic disorders.The project consists of nine clinical trials and two real-world evidence studies. Over 700,000 adult patients worldwide have participated in the program in clinical trials.
Jardiance (O'Tang Jing, Engliazin) is an oral, once-daily, highly selective SGLT-2 inhibitor. SGLT-2 inhibitors have been shown to block the reabsorption of glucose in the kidneys, to excrete too much glucose into the body to reduce blood glucose levels, and the hypoglycemic effect is independent of β cell function and insulin resistance. In addition to its clear hypoglycemic effect, the drug has additional benefits such as reducing weight loss and reducing the risk of cardiovascular events.
Jardiance was approved in 2014 and has been approved for three indications: (1) for the treatment of patients with type 2 diabetes; (2) for patients with concurrent cardiovascular disease, reducing the risk of cardiovascular death, and (3) for reducing the risk of cardiovascular death and heart failure in patients with heart failure (HF).
