Benefiting Patients With Kidney Disease, The First Prescription Of Finerenone Landed

In recent years, the systematic analysis of the Global Burden of Disease (GBD) shows that the age-standardized mortality rate of chronic diseases such as tumors and cardiovascular diseases has reached an inflection point, but the mortality rate of CKD continues to rise, and the disease burden is heavy [1]. Data show that the prevalence of chronic kidney disease (CKD) in China is 10.8%, and the number of patients exceeds 100 million [2]. Diabetes has become an important cause of CKD. About 40% of T2D patients will progress to CKD [3].

Click to Rou Congrong cistanche for kidney disease

The onset of T2D-related CKD is hidden, and renal function gradually deteriorates. Some patients eventually need dialysis to maintain their lives, but more patients fail to enter dialysis and die due to various reasons. Cardiovascular events are the main cause of death in patients. As the world's first new non-steroidal, highly selective mineralocorticoid receptor antagonist (MRA) finerenone was approved for T2D-related CKD, it was officially approved in China on June 29, 2022. Treatment of adult patients with T2D-related CKD.

With the availability of finerenone in China, many Chinese experts have issued the first prescription of finerenone in the field of nephropathy, helping more patients to improve the adverse outcome of kidney and heart as soon as possible. Taking this opportunity, the medical community is particularly honored to invite two authoritative experts from China to discuss the new progress in the disease treatment field, the new upgrade of treatment strategies, and the clinical value and practical guidance brought by the implementation of finerenone prescription.

Create a new era of kidney disease management in China

The issuance of the first finerenone prescription in many hospitals in China, will light up new hope for the vast number of T2D-related CKD patients in China and open a new era of treatment. Experts are also full of expectations for this.

"The clinical treatment of T2D-related CKD needs to take into account the comprehensive management of renal and cardiac risks. Although the standard treatment regimen RASi can delay disease progression to a certain extent, it has limitations, and patients still face high residual risks. There is still huge unmet clinical needs." need.

Finerenone is a brand-new non-steroidal highly selective MRA, which can directly block CKD by fully antagonizing the excessive activation of MR, exerting anti-oxidation, anti-inflammation, and anti-fibrosis effects, focusing on the benefits of the kidneys, and at the same time protecting the cardiovascular system It is believed that it will become a new standard of treatment in the field of kidney disease in the future.

With the first landing of finerenone, we are also very much looking forward to the rapid accumulation of finerenone in clinical practice in China, providing clinicians with a new treatment weapon, and bringing new hope to the majority of T2D-related kidney disease patients! "

"Finerenone has successively published high-quality evidence-based evidence in the past two years. The global large-scale phase III RCT studies FIDELIO and FIGARO were published in the "New England Journal" successively, with over 13,000 people, covering FIDELITY of T2D-related CKD 1-4 patients The pooled analysis confirmed that finerenone has a very significant renal and cardioprotective effect, reducing UACR levels by more than 30%; at the same time, we also saw that the average increase in blood potassium levels was only 0.19mmol/L, and there were no sex hormone-related adverse reactions. The experimental results show that finerenone has both excellent efficacy and good tolerance.

So far, many guidelines in China, including KDIGO and ADA just released this year, have given high-level recommendations for finerenone in category A. With the entry of finerenone into clinical practice in China, we also look forward to the output of more real-world clinical experience and clinical data, which will promote the new upgrade of the overall treatment strategy of the disease, and at the same time benefit the majority of T2D-related kidney disease patients. "

From tradition to innovation, the new MRA unlocks a new pattern of disease treatment

Mineralocorticoid receptor (MR) is a nuclear receptor expressed in tissues/cells throughout the body, including the kidney, heart, and fibroblasts. The pro-inflammatory and pro-fibrotic effects of MR overactivation are key factors in the progression of CKD and increased cardiovascular risk [4]. Therefore, blocking the excessive activation of MR has become an essential part of the treatment of T2D-related CKD patients. Finerenone is a drug developed based on MR targets.

Clinically, MRA is divided into steroidal and non-steroidal. Although there is only one-word difference between the two, there are important differences in molecules, mechanisms of action, and pharmacological properties (Figure 1). Finerenone is a non-steroidal MRA developed based on the structure of dihydropyridine. Compared with traditional steroidal MRAs such as spironolactone, it has stronger affinity, stronger antagonistic effect, and better anti-inflammatory and anti-fibrosis effects; Ketone has a higher selectivity and no sex hormone-related adverse reactions [5]. At the same time, finerenone is evenly distributed in the kidney and heart, has a short half-life, and has no active metabolites, so the risk of hyperkalemia is lower.

As the world's first innovative non-steroidal MRA approved for T2DM-related CKD, finerenone has clear evidence-based evidence of renal and cardiac benefits, and due to its innovative structure, it is potent, highly selective, and high in potassium The clinical application in the real world is highly anticipated.

For kidney and heart benefits, finerenone has been recommended by many Chinese guidelines

Finerenone has received much attention from the outside world, which is inseparable from its clinical superiority in multiple large-scale trials. Among them, the FIDELITY study is by far the largest phase III clinical study in the field of CKD with T2D. The efficacy and safety of CKD progression [6].

A total of 13,171 mild to moderate CKD patients with T2D from 48 countries were included in the study, including 2,894 Asian patients. Based on standard treatment, patients were randomized to receive finerenone 10/20mg (n=6519) or placebo (n=6507) in a 1:1 ratio, and the median follow-up time was 3 years.

From the research results, based on maximizing the treatment of RAS inhibitors, and when the blood pressure and blood sugar of the patients have reached the target, finerenone can still significantly reduce the risk of the renal composite endpoint by 23%, and significantly reduce the risk of cardiovascular composite endpoint up to 14% (Figure 2). In addition, after 4 months of finerenone treatment, the urinary albumin/creatinine ratio (UACR) level of patients was significantly reduced by 32% compared with the placebo group, and the effect continued. In terms of safety, there was no significant difference in the incidence of adverse events in the finerenone group compared with the placebo group, there was no effect on blood sugar and gonads, and only 1.7% of the patients permanently discontinued the drug due to hyperkalemia.

At the 2022 ASN conference, the results of the Chinese subgroup analysis of the FIDELIO study announced by Chinese scholars showed that compared with placebo, finerenone can significantly reduce the relative risk of the composite endpoint of major renal events by 41% (HR=0.59, 95%) CI 0.39-0.88; P=0.009) [7].

The FIDELITY study is a large-scale pooled analysis of two phase iii clinical studies of finerenone - FIDELIO-DKD and FIGARO-DKD. The selected patients cover mild to severe severity (CKD stage 1-4, UACR stage 2-3) T2D-related CKD patients are also very clinically representative in the real world. The results prove that finerenone has shown consistent cardiorenal protection for T2D-related CKD patients of different severity.

The 2022 Guidelines for Improving Global Kidney Disease Outcomes Organization (KDIGO) pointed out that for T2D-related CKD patients, if eGFR ≥ 25ml/min/1.73m2, normal blood potassium, albuminuria still exists after using the maximum tolerable dose of RAS inhibitors ( ACR ≥ 30 mg/g), it is recommended to use non-steroidal MRA finerenone with clear evidence of renal-heart benefit (Grade A recommendation).

Among them, the main points of clinical use are pointed out:

1. Based on the definite evidence of renal-heart benefit, finerenone should be given priority;

2. For T2D with CKD progression and high risk of cardiovascular events (that is, patients who still have persistent proteinuria after using other standard treatments), finerenone is most suitable;

3. In the treatment of T2D-related CKD, it can be considered to combine finerenone based on RASi;

4. Finerenone and SGLT2i mechanisms are complementary, and the combination of the two may have superimposed renal and cardiac benefits, further reducing proteinuria, and the risk of hyperkalemia may be lower[8].

Summary

T2D-related CKD is a health problem of global concern, and the research and development of related innovative drugs are "forced by the situation" and even more "the trend of the times". From high-quality evidence-based to authoritative guideline recommendations, the value of finerenone's renal and cardiac benefits has been continuously verified. The implementation of the prescription of finerenone in the field of nephropathy, it will reshape the new pattern of nephropathy treatment and brighten the better life of patients!

for more information:ali.ma@wecistanche.com