向EMA提交的營銷授權(quán)申請(MAA)和向FDA提交的新藥申請(NDA)均基于來自III期FIDELIO-DKD研究的陽性數(shù)據(jù),這是迄今為止在CKD和T2D方面開展的最大規(guī)模III期臨床試驗項目的一部分。試驗結(jié)果在美國腎臟病學(xué)會(ASN)腎臟周重塑2020(Kidney Week Reimagined 2020)上公布,并于2020年10月同時發(fā)表在《新英格蘭醫(yī)學(xué)雜志》(NEJM)。
Finerenone(BAY 94-8862)是一種研究性、非甾體類、選擇性鹽皮質(zhì)激素受體拮抗劑(MRA)。鹽皮質(zhì)激素受體過度激活是腎臟和心臟損害的主要驅(qū)動因素。在2015年,美國FDA授予了Finerenone快速通道資格(FTD)。
慢性腎臟?。–KD)是糖尿病最常見的并發(fā)癥之一,也是心血管疾病的一個獨立危險因素。在所有II型糖尿病患者中,大約40%的患者會發(fā)展為CKD。CKD是終末期腎病和腎功能衰竭的主要原因,在晚期,患者可能需要透析或腎移植以維生存。在10年時間里,伴有CKD的II型糖尿病患者死于心血管相關(guān)疾病的可能性是單純II型糖尿病患者的3倍。眾所周知,在患有CKD和II型糖尿病的患者中,鹽皮質(zhì)激素受體過度激活會在腎臟和心臟中引發(fā)有害的過程(例如,炎癥和纖維化)。在全球范圍內(nèi),II型糖尿病患者中的CKD是腎功能衰竭的最常見原因。
圖注:Finerenone作用機制
Finerenone III期臨床項目是迄今為止最大的CKD III期臨床項目。該項目由兩項研究組成,入組了全球各地1.3萬例伴有廣泛嚴重程度CKD疾病的T2D患者,包括早期腎損害和更晚期腎病的患者。該項目旨在評估Finerenone與安慰劑分別聯(lián)合標準護理對腎臟和心血管(CV)預(yù)后的影響。
FIDELIO-DKD(Finerenone降低糖尿病腎病腎衰竭和疾病進展)是一項隨機、雙盲、安慰劑對照、平行組、多中心、事件驅(qū)動的III期研究,入組了來自全球48個國家1000多個地點的約5700例伴有CKD的T2D患者。研究中,這些患者被隨機分配,接受每天一次口服10mg或20mg的Finerenone或安慰劑,同時接受標準護理,包括降糖治療和最大耐受劑量的腎素-血管緊張素系統(tǒng)(RAS)阻斷劑,如血管緊張素轉(zhuǎn)換酶(ACE)抑制劑或血管緊張素II受體阻滯劑(ARB)。該研究已經(jīng)達到了主要終點。
FIGARO-DKD(Finerenone降低糖尿病腎病心血管病發(fā)病率和死亡)研究仍在進行中,該研究在歐洲、日本、中國、美國等48個國家入組了約7400例伴有CKD的T2D患者。
拜耳最近宣布啟動FINEARTS-HF研究,這是一項多中心、隨機、雙盲、安慰劑對照III期研究,將在超過5500例左心室射血分數(shù)≥40%的有癥狀心力衰竭(HF)患者(紐約心臟協(xié)會II-IV級)中調(diào)查Finerenone與安慰劑。
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