德國(guó)殷格翰和美國(guó)印第安納波利斯2020年11月2日 /美通社/ -- 勃林格殷格翰和禮來(lái)公司（NYSE：LLY）宣布：EMPEROR-Reduced III期臨床試驗(yàn)新的探索性亞組分析結(jié)果表明，恩格列凈可降低伴或不伴糖尿病、射血分?jǐn)?shù)降低的成年人心力衰竭患者的心血管和腎臟不良事件的風(fēng)險(xiǎn)，無(wú)論其基礎(chǔ)性慢性腎臟疾病情況如何。該結(jié)果已于今天在2020年美國(guó)腎臟病學(xué)會(huì)腎臟周上作為口頭報(bào)告分享，并發(fā)表于Circulation雜志。[1]
EMPEROR 項(xiàng)目臨床研究員、法國(guó)洛林大學(xué)治療領(lǐng)域名譽(yù)教授Faiez Zannad醫(yī)學(xué)博士表示：“心力衰竭和慢性腎臟病本身都與住院和因心血管疾病原因過(guò)早死亡的風(fēng)險(xiǎn)增加有關(guān)。一種疾病的存在通常會(huì)加速另一種疾病的發(fā)作和發(fā)展，進(jìn)一步增加疾病風(fēng)險(xiǎn)，并導(dǎo)致更差的預(yù)后。在EMPEROR-Reduced研究中，對(duì)于伴或不伴慢性腎臟疾病、射血分?jǐn)?shù)降低的成人心力衰竭患者，恩格列凈在降低心血管死亡和心力衰竭而住院的風(fēng)險(xiǎn)（試驗(yàn)的復(fù)合主要終點(diǎn)）上呈現(xiàn)出一致性，同時(shí)延緩患者腎功能下降。對(duì)于越來(lái)越多患有心力衰竭和慢性腎臟疾病的成年患者來(lái)說(shuō)，這是一個(gè)令人鼓舞的消息?！?/p>
如先前報(bào)道，EMPEROR-Reduced臨床研究顯示，對(duì)于伴或不伴糖尿病、射血分?jǐn)?shù)降低的成人心力衰竭患者，恩格列凈可將心血管死亡事件或因心衰而住院的相對(duì)風(fēng)險(xiǎn)降低25%，將首次和再次因心衰而住院的相對(duì)風(fēng)險(xiǎn)降低30%，且患者的eGFR（衡量腎功能下降的指標(biāo)）下降更慢（試驗(yàn)的復(fù)合終點(diǎn)）。[1] 另一項(xiàng)探索性分析表明，恩格列凈使復(fù)合腎臟終點(diǎn)的相對(duì)風(fēng)險(xiǎn)降低50%，包括終末期腎臟疾病或腎臟功能?chē)?yán)重喪失。[1]對(duì)于伴或不伴基礎(chǔ)性慢性腎臟疾病患者亞組人群中，包括嚴(yán)重腎損傷患者，在這項(xiàng)新分析中的所有終點(diǎn)中都觀察到了這些獲益。[1]在所有參與EMPEROR-Reduced臨床試驗(yàn)的患者中，其安全性與恩格列凈的已知安全性相似。[2]
勃林格殷格翰公司副總裁、心臟代謝領(lǐng)域醫(yī)學(xué)負(fù)責(zé)人Waheed Jamal博士表示：“我們對(duì)心力衰竭和慢性腎臟疾病之間的相互作用已經(jīng)有了很好的了解，但是我們還需要對(duì)如何治療這些相互關(guān)聯(lián)的疾病有更深入的了解。這項(xiàng)新數(shù)據(jù)證明了對(duì)心-腎-代謝疾病進(jìn)行全面管理的益處，具有改善全球數(shù)百萬(wàn)人健康的潛力。”
禮來(lái)公司產(chǎn)品開(kāi)發(fā)副總裁Jeff Emmick博士表示：“心力衰竭和慢性腎臟疾病是一種常見(jiàn)的、威脅生命的疾病，其治療方案需要得到改進(jìn)。EMPOWER臨床開(kāi)發(fā)計(jì)劃，包括我們正在進(jìn)行的EMPEROR-Preserved和EMPA-KIDNEY試驗(yàn)，探索恩格列凈在改善這些疾病患者的預(yù)后中發(fā)揮的潛在作用。EMPEROR-Reduced的新研究結(jié)果將幫助我們實(shí)現(xiàn)重新定義如何治療這些患者的目標(biāo)。”
2020年3月，美國(guó)食品藥品監(jiān)督管理局（FDA）授予恩格列凈快速通道資格，用于治療慢性腎臟疾病，這顯示了該疾病患者迫切需要新的治療選擇。快速通道資格涵蓋了正在進(jìn)行的EMPA-KIDNEY試驗(yàn)，該試驗(yàn)正在研究恩格列凈對(duì)患有慢性腎臟疾?。ɑ加谢蛘卟换加刑悄虿。┑某扇酥袑?duì)腎臟疾病進(jìn)展和心血管死亡發(fā)生的影響。 EMPA-KIDNEY臨床試驗(yàn)結(jié)果預(yù)計(jì)于2022年公布。[2]
2019年6月，F(xiàn)DA還于授予恩格列凈快速通道資格，用于降低慢性心衰患者的心血管死亡與心衰住院風(fēng)險(xiǎn)。快速通道資格基于EMPEROR項(xiàng)目，該項(xiàng)目包括 EMPEROR-Reduced 與EMPEROR-Preserved 臨床研究。EMPEROR-Preserved正在研究恩格列凈對(duì)射血分?jǐn)?shù)保留的心力衰竭成年人的心血管死亡或因心力衰竭住院的影響，該領(lǐng)域目前尚無(wú)獲批的治療選擇。EMPEROR-Preserved結(jié)果預(yù)計(jì)將于2021年公布。恩格列凈尚不適用于治療心力衰竭。
EMPEROR和EMPA-KIDNEY研究是EMPOWER臨床項(xiàng)目的一部分，EMPOWER是所有SGLT2抑制劑中最廣泛和最全面的試驗(yàn)之一，旨在探索恩格列凈對(duì)各種心臟-腎臟-代謝疾病患者生活的影響。
關(guān)于EMPEROR心力衰竭研究[6],[3]
EMPEROR（采用恩格列凈治療慢性心衰患者的結(jié)局試驗(yàn)）慢性心衰研究包括兩項(xiàng)III期、隨機(jī)、雙盲試驗(yàn)，針對(duì)射血分?jǐn)?shù)保留與射血分?jǐn)?shù)降低的成人慢性心衰患者（均包括伴與不伴糖尿病的患者），在接受標(biāo)準(zhǔn)治療的基礎(chǔ)上，研究每日一次恩格列凈與安慰劑相比的療效與安全性：
主要終點(diǎn)：至首次被裁定為心血管死亡事件或被裁定為因心衰（HHF）而住院的時(shí)間
入組患者人數(shù)：3730例
完成時(shí)間：2020年
主要總結(jié)鏈接
主要終點(diǎn)：至首次被裁定為心血管死亡事件或被裁定為因心衰（HHF）而住院的時(shí)間[時(shí)間范圍：最長(zhǎng)38個(gè)月]
預(yù)期入組患者數(shù)量：約5,990例
預(yù)計(jì)完成時(shí)間：2021年
*射血分?jǐn)?shù)是表示每次收縮時(shí)左心室泵出的血液百分比的測(cè)量值。當(dāng)心臟舒張時(shí)，心室重新充滿血液。
關(guān)于EMPOWER項(xiàng)目
聯(lián)盟開(kāi)發(fā)了EMPOWER項(xiàng)目，旨在探索恩格列凈對(duì)一系列心臟-腎臟-代謝疾病的主要臨床心血管和腎臟結(jié)局的影響。心腎代謝疾病是全球死亡的主要原因，每年導(dǎo)致的死亡病例高達(dá)2000萬(wàn)。[9] 通過(guò)EMPOWER項(xiàng)目，勃林格殷格翰和禮來(lái)正在努力增加對(duì)這些互聯(lián)系統(tǒng)的認(rèn)知，并開(kāi)發(fā)可提供綜合、多器官獲益的治療。[10]EMPOWER由9項(xiàng)研究和一項(xiàng)真實(shí)世界研究組成，EMPEROR強(qiáng)化了聯(lián)盟對(duì)改善心臟-腎臟-代謝疾病患者臨床治療結(jié)局的長(zhǎng)期承諾。臨床研究全球入組超過(guò)257,000位成人患者，EMPOWER是迄今為止針對(duì)SGLT2抑制劑開(kāi)展的最廣泛和最全面的臨床項(xiàng)目之一。
開(kāi)發(fā)項(xiàng)目包括以下試驗(yàn)：
[1]Composite exploratory endpoint included chronic dialysis or renal transplant or sustained reduction of ≥40% in eGFR (CKD-EPI) or a sustained eGFR <15 mL/min/1.73 m2 (for patients with baseline eGFR ≥30) or sustained eGFR <10 mL/min/1.73 m2 (for patients with baseline eGFR <30 mL/min/1.73 m2). |
[1] Packer M, Anker SD, Butler J, et al. Cardiac and Renal Outcomes With Empagliflozin in Heart Failure With a Reduced Ejection Fraction. N Engl J Med. 2020;10.1056/NEJMoa2022190. |
[2] ClinicalTrials.gov. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). Available at: https://clinicaltrials.gov/ct2/show/NCT03594110. Accessed October 2020. |
[3] ClinicalTrials.gov. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03057977. Accessed October 2020. |
[4] ClinicalTrials.gov. EMPagliflozin initiated in patients hospitalised for acUte heart faiLure (de novo or decompensated chronic HF) who have been StabilisEd (EMPULSE) Available at: https://www.clinicaltrials.gov/ct2/show/NCT04157751. Accessed October 2020. |
[5] Boehringer Ingelheim Pharmaceuticals, Inc. Press release. 2020. Available at: https://www.boehringer-ingelheim.com/press-release/dcri-collaboration-empact-mi. Accessed October 2020. |
[6] ClinicalTrials.gov. A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with reduced Ejection Fraction (HFrEF) (EMPERIAL - reduced). Available at: https://clinicaltrials.gov/ct2/show/NCT03448419. Accessed October 2020. |
[7] ClinicalTrials.gov. A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, in patients with chronic HeArt FaiLure with preserved Ejection Fraction (HFpEF) (EMPERIAL - preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03448406. Accessed October 2020. |
[8] Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117-28. |
[9] Kim DJ, Sheu WH-H, Seino Y, et al. Cardiovascular Effectiveness and Safety of Empagliflozin in Routine Care in East Asia: Results from the EMPRISE study. Presented at IDF Congress 2019. 2-6 December 2019, Busan, Korea. |
[10] Patorno E, Pawar A, Franklin J, et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Trial. Circulation. 2019;139:2822-30. |
[11] American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: August 2020. |
[12] GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789-1858. |
[13] Suskin N, McKelvie RS, Burns RJ, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J. 2000;21:1368-75. |
[14] Ronco C, McCullough P, Anker SD, et al. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Eur Heart J. 2010;31(6):703-11. |
[15] Lazzeri C, Valente S, Tarquini R, et al. Cardiorenal syndrome caused by heart failure with preserved ejection fraction. Int J Nephrol. 2011;2011:634903. |
[16] Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: May 2020. |
[17] European Summary of Product Characteristics Jardiance®, approved May 2018. Data on file. |
[18] Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017. |
[19] Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: August 2020. |
[20] Jardiance® (empagliflozin) tablets. European Product Information; approved April 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Accessed October 2020. |
[21] Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017. |
[22] Vallon V and Thompson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215–25. |
