Major Milestone: Jardiance® (Empagliflozin) Approved in China for Treatment of Chronic Kidney Disease in Adults

－The approval of this indication is based on the EMPA-KIDNEY clinical trial. The results showed that, in a broad population of chronic kidney disease (CKD) patients at risk of disease progression, treatment with empagliflozin reduced the relative risk of kidney disease progression or cardiovascular death by 28% and reduced the relative risk of hospitalization for any cause by 14%, which was statistically significant (HR: 0.86; 95% CI 0.78-0.95; P=0.0025 [absolute risk reduction 4.4%]) compared to the placebo group. The trial demonstrated that the overall safety data were generally consistent with previous studies, confirming the safety of empagliflozin. Furthermore, the effect of empagliflozin on CKD was independent of the patient's diabetes status and effective across patients with varying ranges of eGFR1,2.

－According to statistics, the prevalence rate of CKD in China is 8.2%, with approximately 82 million adult CKD patients.

- This CKD indication is another new indication for Jardiance® approved in China, following adult type 2 diabetes, heart failure with reduced ejection fraction in adults, heart failure with preserved ejection fraction in adults, and combination insulin therapy for type 2 diabetes.

On November 24, 2023, Eli Lilly and Company and Boehringer Ingelheim jointly announced that the new indication for their diabetes alliance’s SGLT2 inhibitor Jardiance® (empagliflozin) has been approved by the National Medical Products Administration of China for the treatment of chronic kidney disease (CKD) in adults.This is another new indication for Jardiance® approved in China, following adult type 2 diabetes, heart failure with reduced ejection fraction in adults, heart failure with preserved ejection fraction in adults, and combination insulin therapy for type 2 diabetes. Together with the existing indications for type 2 diabetes and heart failure, Jardiance® helps manage risks associated with cardio-renal-metabolic diseases. Since its launch, it has benefited more than 1 billion patients globally.

As a globally recognized public health issue, CKD (Chronic Kidney Disease) is typically progressive, characterized by a decline in estimated glomerular filtration rate (eGFR) and high albuminuria. Statistics indicate that there are approximately 850 million CKD patients worldwide. Data shows that between 2018 and 2019, about 82 million adults in China were CKD patients. Due to the insidious onset of CKD, the rates of early diagnosis and treatment are low. Millions of people die prematurely each year from chronic kidney disease and related complications. Once CKD progresses to end-stage kidney disease (ESKD), patients require renal replacement therapy (including hemodialysis, peritoneal dialysis, or kidney transplantation) to sustain life, which not only severely impacts the quality of life but also serves as one of the leading causes of poverty.

The approval of the new indication for Jardiance® is based on the EMPA-KIDNEY clinical trial, the largest and most extensive SGLT2 inhibitor trial conducted to date in patients with CKD. The trial demonstrated significant benefits of empagliflozin in patients with chronic kidney disease, reducing the relative risk of kidney disease progression or cardiovascular death by 28% compared to placebo (HR: 0.72; 95% CI: 0.64-0.82; P<0.000001 [absolute risk reduction: 3.8%]). The trial also showed that empagliflozin reduced the relative risk of hospitalization for any cause by 14% compared to placebo, a result that was statistically significant (HR: 0.86; 95% CI: 0.78-0.95; P=0.0025 [absolute risk reduction: 4.4%])1,2. The overall safety data from the trial were consistent with findings from previous studies, confirming the safety of empagliflozin1,2. CKD doubles an individual's risk of hospitalization11,12. According to research, in 2016, CKD patients accounted for 4.86% of total hospitalized patients in China, with nearly one million patients, and annual medical expenses amounted to 27.646 billion yuan, accounting for 6.5% of total medical costs that year13.

Academician of the Chinese Academy of Engineering
Director of the National Clinical Research Center for Kidney Diseases
Professor Liu Zhihong stated

Chronic kidney disease (CKD) is a major threat to public health worldwide. In China, due to improvements in public education, healthcare services, and environmental protection over the past decade, the prevalence of CKD among adults aged 18 and above has decreased from 10.8% to 8.2%. However, due to the "three highs and three lows" characteristics of CKD—high incidence, high rate of cardiovascular comorbidities, high mortality and disability rates; low awareness, low consultation rates, and low control rates—patients, their families, and society still face a significant burden. Encouragingly, China participated in the large-scale clinical study EMPA-KIDNEY, enrolling 986 Chinese CKD patients, accounting for 15% of the global enrollment. This means that the data can be applied clinically at the earliest opportunity, allowing Chinese patients to benefit earlier from innovative drugs. This approval brings a safe and effective new treatment option, Jardiance®, to Chinese patients, with the potential to improve the treatment prospects for more CKD patients.

President and General Manager of Eli Lilly China
Bei Liming stated

We are delighted to see that Jardiance® has further expanded its indications in China, bringing good news to more Chinese patients.

Currently, Jardiance® has covered multiple unmet therapeutic areas, including type 2 diabetes, cardiovascular, renal, and metabolic diseases. The approval of this new indication once again establishes its significant treatment position in the cardio-renal metabolic disease field. In the future, we will continue to extend the benefits of this therapy to more patients in China, continuously contributing to the realization of the grand blueprint of 'Healthy China 2030'.

General Manager of Boehringer Ingelheim Greater China Region Human Medicine Business
Chen Xingrong stated

The latest approval of Jardiance® for a new indication in China marks another successful milestone, offering doctors and patients a new treatment option and representing a significant achievement for this innovative drug. This not only reflects the strong endorsement of the product by Chinese drug regulatory authorities but also demonstrates its lasting impact. We will continue to prioritize patients, explore unmet clinical needs, and deliver transformative innovative drugs and solutions to benefit a wide range of patients across China, bringing long-term benefits to patients and their families.

About EMPA-KIDNEY:
Research on the Cardioprotective and Renoprotective Effects of Empagliflozin1,2,8

EMPA-KIDNEY (NCT03594110) is a multinational, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the impact of empagliflozin on the progression of kidney disease and the risk of cardiovascular death. EMPA-KIDNEY is the largest and most extensive SGLT2 inhibitor trial conducted to date for CKD. The trial included 6,609 participants with a wide range of underlying etiologies, many of whom had comorbidities such as cardiovascular, renal, or metabolic diseases. Results from the EMPA-KIDNEY trial indicate that empagliflozin provides benefits for adult patients at risk of kidney disease progression, including those with or without diabetes and with varying levels of kidney function. The primary outcome was a composite of cardiovascular death or the first event of kidney disease progression, with the first event of kidney disease progression defined as end-stage kidney disease (requiring kidney replacement therapy such as dialysis or kidney transplantation), sustained decline in eGFR to <10 mL/min/1.73m², renal death, or sustained decline in eGFR by ≥40% since randomization. Key secondary endpoints included a composite of cardiovascular death or hospitalization for heart failure, all-cause hospitalization, and all-cause mortality. EMPA-KIDNEY included 6,609 adult CKD patients randomly selected from eight countries, with or without diabetes, and with or without proteinuria. Participants received 10 mg of empagliflozin or placebo in addition to current standard of care.

About Chronic Kidney Disease

Chronic kidney disease affects approximately 850 million people worldwide, accounting for more than 10% of the total population. This disease is caused by progressive damage to the kidneys, rendering them unable to function properly. As the majority of patients are asymptomatic until the late stages of the condition, most remain undiagnosed, leading to millions of premature deaths annually from chronic kidney disease and related complications. The Boehringer Ingelheim and Eli Lilly and Company alliance is committed to delivering transformative treatments for patients with chronic kidney disease and other cardio-renal-metabolic conditions.

About Cardio-Renal-Metabolic Diseases

Boehringer Ingelheim and Eli Lilly are committed to bringing transformative treatments to patients with cardio-renal-metabolic diseases, a group of interconnected conditions that affect more than 1.4 billion people worldwide and are the leading cause of death15,16.

The cardiovascular, renal, and metabolic systems are interrelated, sharing common risk factors and pathological pathways in their progression. Dysfunction in one system may accelerate the onset of diseases in others, contributing to the progression of interconnected conditions such as type 2 diabetes, cardiovascular disease, heart failure, and kidney disease, which in turn increases the risk of cardiovascular mortality. Conversely, improvement in one system can positively impact the others.

Through our research and treatment, our goal is to support human health by restoring the balance between the cardio-renal-metabolic systems and reducing the risk of severe complications. As part of our commitment to those whose health is threatened by cardio-renal-metabolic diseases, we will continue to adopt a multidisciplinary approach and focus our resources on filling therapeutic gaps.

About Empagliflozin

Empagliflozin (brand name: Jardiance®) is an oral, once-daily, highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor. It is also the first type 2 diabetes drug in many countries’ prescribing information to include data on reducing the risk of cardiovascular death. In China, the indications for empagliflozin are adult type 2 diabetes, heart failure, and most recently, chronic kidney disease.

About Eli Lilly and Company and Boehringer Ingelheim

Boehringer Ingelheim and Eli Lilly Alliance Leverages the Strengths of Two World-Leading Pharmaceutical Companies. By Collaborating, the Two Companies Are Committed to Helping Patients with Type 2 Diabetes and Dedicated to Addressing Unmet Medical Needs in Areas Such as Heart Failure and Chronic Kidney Disease.

About Eli Lilly and Company

Eli Lilly and Company is a globally leading pharmaceutical company engaged in the research, development, manufacturing, and marketing of medicines, dedicated to improving human health through innovation. Eli Lilly and Company was founded more than a century ago by Colonel Eli Lilly in Indianapolis, Indiana, USA, with a commitment to producing high-quality medicines to meet genuine medical needs. Today, we remain steadfast in this mission and continue our work based on it. Around the world, our employees are constantly striving to develop drugs that can make a difference in people's lives and make them available to patients who truly need them. Moreover, we are committed to enhancing public understanding of diseases and improving disease management, while giving back to society through charitable efforts and volunteer activities. Guided by the principle of "Rooted in China, Benefiting China," Eli Lilly is expanding its business in China and holds a leading position in areas such as diabetes, oncology, immunology, pain management, and neurodegenerative diseases. For more information about Eli Lilly and Company, please visit: www.lilly.com

About Boehringer Ingelheim

Boehringer Ingelheim is dedicated to researching breakthrough therapies aimed at transforming lives and safeguarding the health of generations to come. As a global leader in biopharmaceuticals driven by innovation, the company delivers value through pioneering solutions in areas of high unmet medical need. Since its founding in 1885, Boehringer Ingelheim has remained an independent, family-owned business with a long-term focus on sustainability. With over 53,000 employees worldwide, the company serves more than 130 regions across its two core businesses: human pharmaceuticals and animal health. For more information, please visit: www.boehringer-ingelheim.com

References
1.EMPA-KIDNEYfulldatapresentation,presentedon4November2022attheAmericanSocietyofNephrology(ASN)Congress2022-KidneyWeek.
2.HerringtonW,StaplinN,WannerC,etal.EmpagliflozininPatientswithChronicKidneyDisease.NEnglJMed.2023;388:117-127.
3.WangL,XuX,ZhangM,HuC,ZhangX,LiC,NieS,HuangZ,ZhaoZ,HouFF,ZhouM.PrevalenceofChronicKidneyDiseaseinChina:ResultsFromtheSixthChinaChronicDiseaseandRiskFactorSurveillance.JAMAInternMed.2023Apr1;183(4):298-310.
4.Schechter,M.etal.CardiovascDiabetol.2022:21;104.
5.LiP,etal.BrazJMedBiolRes.2020;53(3):e9614.
6. Meng Lingdong, Liu Changhua, Wu Gang. Research progress in chronic kidney disease [J]. Shanxi Medical Journal, 2017, 46(10): 1170-1172.
7.ClinicalTrials.EMPA-KIDNEY(TheStudyofHeartandKidneyProtectionWithEmpagliflozin).Availableat:https://clinicaltrials.gov/ct2/show/NCT03594110.Accessed:June2023.
8.CoreshJ.UpdateontheBurdenofCKD.JAmSocNephrol.2017;28(4):1020–1022.
9.LuyckxV,etal.BullWorldHealthOrgan.2018;96(6):414–422D.
10. Professional Committee of Kidney Disease Prevention and Control, Chinese Preventive Medicine Association. Chinese Journal of Internal Medicine. 2023, 62(8): 4-32
11.USRDS.2021AnnualReport.Availableat:https://usrds-adr.niddk.nih.gov/2021/chronic-kidney-disease/3-morbidity-and-mortality-in-patients-with-ckd.Accessed:July2023.
12.BikbovB,etal.Global,regional,andnationalburdenofchronickidneydisease,1990–2017:asystematicanalysisfortheGlobalBurdenofDiseaseStudy2017.Lancet.2020;395(10225):709-733.
13. Writing Group of "China Cardiovascular Health and Disease Report". Key Points Interpretation of "China Cardiovascular Health and Disease Report 2020" [J]. Chinese Journal of Cardiology, 2021, 26(3):10. DOI:10.3969/j.issn.1007-5410.2021.03.001.
14.ZhangL,etal.PrevalenceofchronickidneydiseaseinChina:across-sectionalsurveyLancet,2012,379(9818):815-822.
15.Schechter,M.etal.CardiovascDiabetol.2022:21;104.
16.SundströmJ,etal.CaReMeCKD.LancetRegHealthEur.2022Jun30;20:100438.
17.ThomasM,CooperM,ZimmetP.Changingepidemiologyoftype2diabetesmellitusandassociatedchronickidneydisease.NatRevNephrol.2015;12:73–81.
18.García-DonaireA,RuilopeM.CardiovascularandRenalLinksalongtheCardiorenalContinuum.IntJNephrol.2011:975782.
19.LeonM,MaddoxM.Diabetesandcardiovasculardisease:Epidemiology,biologicalmechanisms,treatmentrecommendationsandfutureresearch.WorldJDiabetes.2015;6(13):1246–58.
20.Jardiance®(empagliflozin)tablets.EuropeanProductInformation,approvedApril2020.Availableat:https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf.Lastaccessed:October2022.

Editor: Baiji

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