Kerendia是第一个在CKD合并T2D的患者中显示出积极的肾脏和心血管结局的非甾体类选择性MRA。
2021年7月10日，美国食品和药物管理局(FDA)已批准Kerendia(finerenone)可降低成人肾小球滤过率(eGFR)持续下降、终末期肾病、心血管死亡、非致死性心肌梗死(MI)和因心力衰竭住院的风险患有与2型糖尿病(T2D)相关的慢性肾病(CKD)的患者。
Kerendia是一种非甾体选择性盐皮质激素受体(MR)拮抗剂，通过阻断上皮（例如肾脏）和非上皮（例如心脏和血管）组织中MR介导的钠重吸收和MR过度激活而起作用。盐皮质激素受体过度激活被认为会导致纤维化和炎症。
该批准基于来自多中心、双盲、安慰剂对照的3期FIDELIO-DKD试验（ClinicalTrials.gov 标识符：NCT02540993）的数据，该试验在5674中评估了finerenone的疗效和安全性以及护理标准CKD患者与2型糖尿病相关。患者被随机分配1:1接受finerenone或安慰剂。
主要复合终点是首次发生肾衰竭的时间、eGFR从基线持续下降至少40%或肾性死亡的时间。关键的次要复合终点是首次发生心血管原因死亡、非致死性心肌梗死、非致死性卒中或因心力衰竭住院的时间。
结果显示，在中位随访2.6年后，主要结局事件发生在Finerenone组17.8%的患者（n=504/2833），而安慰剂组为21.1%的患者（n=600/2841）差（风险比 [HR] 0.82；95% CI，0.73-0.93；P=.001）。Finerenone治疗也与次要结局事件的发生率降低相关（13% [n=367/2833] vs 14.8% [n=420/2841]，安慰剂组；HR 0.86；95% CI，0.75-0.99；P=.034)。 Finerenone 最常见的不良反应是高钾血症、低血压和低钠血症。
“尽管接受了标准的护理治疗以控制血压和血糖，但参与支持 Kerendia 批准的试验的患者群体仍有慢性肾脏疾病进展的风险，”芝加哥大学和 FIDELIO- 负责人 George Bakris 说。 DKD研究调查员。 “在患有与2型糖尿病相关的慢性肾病患者中，医生现在有了一种新的治疗方法来提供肾脏保护。”
Kerendia以10毫克和20毫克片剂的形式提供，装在 30和90支瓶中，预计将于2021年7月末上市。
信息来源：https://www.businesswire.com/news/home/20210709005441/en/Bayer%E2%80%99s-KERENDIA%C2%AE-finerenone-Receives-U.S.-FDA-Approval-for-Treatment-of-Patients-with-Chronic-Kidney-Disease-Associated-with-Type-2-Diabetes
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Generic Name & Formulations:
Finerenone 10mg, 20mg; tabs.
Company:
Bayer Corporation
Indications for: KERENDIA
To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.
Adult Dosage:
See full labeling. Swallow whole. If unable to swallow, tabs may be crushed and mixed with water or soft foods (eg, applesauce). eGFR (≥60mL/min/1.73m2): initially 20mg once daily; (≥25–<60mL/min/1.73m2): initially 10mg once daily; (<25mL/min/1.73m2): not recommended. Target dose: 20mg/day. Dose adjustment based on current serum K+ and current dose: if >5.5mEq/L, withhold dose and restart (for current 20mg/day dose) or consider restarting at 10mg once daily (for current 10mg/day dose) when serum K+ ≤5.0mEq/L; if >4.8–5.5mEq/L, maintain at current dose; if ≤4.8mEq/L, increase to 20mg once daily if current dose is 10mg once daily (if eGFR decreased by >30%, maintain dose at 10mg) or maintain at 20mg if current dose is 20mg once daily.
Children Dosage:
<18yrs: not established.
KERENDIA Contraindications:
Concomitant strong CYP3A4 inhibitors (eg, itraconazole). Adrenal insufficiency.
KERENDIA Warnings/Precautions:
Increased risk of hyperkalemia with decreasing kidney function and higher baseline K+ levels. Measure serum K+ and eGFR prior to initiation. Do not initiate if serum K+ is >5.0mEq/L. Measure serum K+ 4 weeks after initiation, periodically during treatment, and after dose adjustments. Severe hepatic impairment: avoid. Moderate hepatic impairment: consider more monitoring of serum K+. Pregnancy. Nursing mothers: not recommended (during and for 1 day after treatment).
KERENDIA Classification:
Nonsteroidal mineralocorticoid receptor antagonist (MRA).
KERENDIA Interactions:
See Contraindications. |
