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基于模型的药物开发,从皮下注射到静脉注射Secukinumab剂量的桥梁:在牛皮关节炎和轴性脊柱关节炎中获得批准
Thomas Dumortier1, Guillermo Valenzuela2, Melvin Churchill3
1Novartis Pharma AG, Basel, Switzerland.
Clinical pharmacology and therapeutics
|June 2, 2025
概括
针对牛皮关节炎 (PsA) 和轴性脊柱关节炎 (axSpA) 开发了一种新的静脉注射sequinumab剂量方案. 这种方案,每4周输入1.75 mg/kg,与批准的皮下暴露相匹配,并预测类似的疗效和安全性.
科学领域:
- 药理动力学和药理动力学
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
背景情况:
- 塞库金纽马布通过皮下注射被批准用于治疗牛皮关节炎 (PsA) 和轴性脊柱关节炎 (axSpA).
- 研究了一种静脉注射 (IV) 配方,以潜在地提高患者的方便性.
- 最初的静脉注射剂量 (3mg/kg) 显示暴露率高于已批准的皮下注射 (SC) 方案,这促使进一步调查.
研究的目的:
- 为了确定IVseukinumab剂量方案,稳定状态暴露与已批准的SC疗法 (300和150毫克每4周).
- 通过建模和模拟,预测这种新型IV治疗方案对PsA和axSpA患者的疗效和安全性.
- 为了支持监管机构对IV疗法的批准,基于外推数据.
主要方法:
- 来自15个PsA或axSpA临床试验的汇总数据的群体药理动力学 (popPK) 分析.
- 建模和模拟,以确定一种IV疗法,其暴露与批准的SC剂量相比较.
- 暴露-反应分析,以预测拟议的IV治疗方案的疗效和安全性.
主要成果:
- 每4周一次 (q4w) 输入1.75 mg/kg的secukinumab疗法,随着可选的6 mg/kg的负载剂量,在批准的SC疗法范围内实现了稳定状态暴露.
- 从SC疗法的疗效和安全数据的推断得到了暴露-反应建模的支持.
- 确定的IV疗法被FDA批准用于PsA和axSpA治疗,尽管在临床试验中没有直接测试.
结论:
- 1.75 mg/kg IV secukinumab q4w 疗法提供了与已批准的 PsA 和 axSpA 的 SC 配方相比较的暴露.
- 建模和模拟提供了一种可靠的方法来预测疗效和安全性,使新的剂量策略能够获得监管部门的批准.
- 这种静脉注射疗法对患有PsA和axSpA的患者来说是一个潜在的更方便的治疗选择.
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