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基于模型的药物研发方法支持阿达木单抗(修美乐)获批用于治疗青少年化脓性汗腺炎:监管视角。

Model-Informed Drug Development Approach Supporting Approval of Adalimumab (HUMIRA) in Adolescent Patients with Hidradenitis Suppurativa: a Regulatory Perspective.

机构信息

Office of Clinical Pharmacology, Office of Translational Sciences, New Hampshire, USA.

Division of Dermatology and Dental Products, Office of New Drug, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.

出版信息

AAPS J. 2019 Jul 19;21(5):91. doi: 10.1208/s12248-019-0363-5.

Abstract

On October 16, 2018, FDA expanded the adalimumab dosing regimen to adolescent hidradenitis suppurativa (HS) patients 12 years and older, weighing at least 30 kg without new clinical data. This approval was mainly supported by the model-informed drug development approach. Population pharmacokinetic simulations suggest body weight-tiered dosing regimens in adolescent patients will achieve similar exposure to adult patients across all weight range. Adalimumab has a well-established, 16-year long-term safety profile in various diseases in adult and pediatric populations. Current data of adalimumab in the pediatric population demonstrate no exposure-response relationship for adverse events. The effectiveness in adolescent patients was extrapolated from two adequate and well-controlled phase 3 studies in adult patients, assuming similar positive exposure-efficacy relationships in adults and adolescents. This article provides the insight of the application of MIDD on the adalimumab approval in adolescent HS patients and its implication on drug development and regulatory decision especially for pediatrics or rare diseases.

摘要

2018 年 10 月 16 日,FDA 扩大了阿达木单抗的给药方案,适用于 12 岁及以上、体重至少 30kg 的青少年化脓性汗腺炎(HS)患者,无需新的临床数据。这一批准主要基于模型引导药物开发方法。群体药代动力学模拟表明,青少年患者的体重分层给药方案将在所有体重范围内实现与成年患者相似的暴露水平。阿达木单抗在成人和儿科人群中的各种疾病中具有 16 年的良好长期安全性。目前在儿科人群中阿达木单抗的数据表明,不良事件与暴露无相关性。青少年患者的疗效是从两项成人患者充分和良好对照的 3 期研究中推断出来的,假设成人和青少年的阳性暴露-疗效关系相似。本文提供了将 MIDD 应用于阿达木单抗在青少年 HS 患者中的批准的见解,以及对药物开发和监管决策的影响,特别是儿科或罕见疾病。

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