肿瘤药物的后续适应症:肿瘤药物的后续适应症:途径、时间表和《通货膨胀削减法》。

IF 2 4区 医学 Q4 MEDICAL INFORMATICS
Julie A Patterson, James Motyka, Rayan Salih, Robert Nordyke, John M O'Brien, Jonathan D Campbell
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引用次数: 0

摘要

导言:最近的研究对《通货膨胀削减法案》的药品价格谈判计划(DPNP)可能产生的意外后果提出了质疑,认为该法案规定的时限可能会降低制造商投资于批准后研究以获得更多适应症的积极性。鉴于多适应症在扩大癌症患者治疗选择方面的作用,与 IRA 相关的开发激励机制的变化与肿瘤学尤其相关。本研究旨在描述一组新近获批的多适应症肿瘤药物在药物层面上的异质性轨迹和后续适应症的时间表,包括总体情况、以新增适应症的时间和速度为特征的药物亚组以及药物类型(即小分子药物与生物制剂药物):这项横断面研究评估了 2008 年至 2018 年美国 FDA 首次批准的肿瘤药物,这些药物后来被批准用于一种或多种附加适应症。在药物层面记录了后续适应症的数量、类型和批准时间,并根据批准后的开发节奏(即 "快速节奏 "到 "稳健节奏")将药物按四分位数分组:多适应症肿瘤药物(N = 56/86,65.1%)的一个或多个后续适应症获得了新的批准:癌症类型(60.7%)、治疗方法(50.0%)、联合用药(41.1%)、突变(32.1%)或分期(28.6%)。FDA 批准适应症的间隔时间中位数从 "快节奏 "组的 0.6 年(IQR:0.48,0.74)分别增加到 "中度"、"中度测量 "和 "测量 "组的 1.6 年(IQR:1.32,1.66)、2.4 年(IQR:2.29,2.61)和 4.9 年(IQR:3.43,6.23)。速度快 "组的药物通常在首次批准后 9 个月内获得首个后续适应症批准(中位数:0.7 年;IQR:0.54,1.59),而 "速度适中 "组则需要 5.7 年(IQR:3.43,6.98)。在所有多适应症药物中,最近一次获得后续适应症批准的时间中位数为 5.5 年(IQR:3.18, 7.95)。四分之一(25%)的药物在符合 DPNP 资格的时间之后才被批准用于最近的后续适应症:肿瘤新药的批准历史表明,批准后适应症在将治疗选择扩展到新的癌症类型、分期、品系、组合和突变方面发挥了作用。不同的临床开发路径让我们了解到与 IRA 相关的、围绕批准后研究与开发的变化可能带来的意外后果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Subsequent Indications in Oncology Drugs: Pathways, Timelines, and the Inflation Reduction Act.

Introduction: Recent research has raised questions about potential unintended consequences of the Inflation Reduction Act's Drug Price Negotiation Program (DPNP), suggesting that the timelines introduced by the law may reduce manufacturer incentives to invest in post-approval research towards additional indications. Given the role of multiple indications in expanding treatment options in patients with cancer, IRA-related changes to development incentives are especially relevant in oncology. This study aimed to describe heterogeneous drug-level trajectories and timelines of subsequent indications in a cohort of recently approved, multi-indication oncology drugs, including overall, across subgroups of drugs characterized by the timing and pace of additional indications, and by drug type (i.e., small molecule vs. biologic).

Methods: This cross-sectional study evaluated oncology drugs first approved by the FDA from 2008 to 2018 and later approved for one or more additional indications. Numbers, types, and approval timelines of subsequent indications were recorded at the drug level, with drugs grouped by quartile based on the pacing of post-approval development (i.e., "rapid pace" to "measured pace").

Results: Multi-indication oncology drugs (N = 56/86, 65.1%) had one or more subsequent indication approved in a new: cancer type (60.7%), line of treatment (50.0%), combination (41.1%), mutation (32.1%), or stage (28.6%). The median time between FDA approvals for indications increased from 0.6 years (IQR: 0.48, 0.74) in the "rapid pace" group to 1.6 years (IQR: 1.32, 1.66), 2.4 years (IQR: 2.29, 2.61), and 4.9 years (IQR: 3.43, 6.23) in the "moderate," "measured-moderate," and "measured" pace groups, respectively. Drugs in the "rapid pace" group often received their first subsequent indication approval within 9 months of initial approval (median: 0.7 years; IQR: 0.54, 1.59), whereas the "measured pace" group took a median of 5.7 years (IQR: 3.43, 6.98). Across all multi-indication drugs, the median time to the most recent approval for a subsequent indication was 5.5 years (IQR: 3.18, 7.95). One quarter (25%) of drugs were approved for their most recent subsequent indication after the time at which they would be DPNP-eligible.

Conclusion: Approval histories of new oncology drugs demonstrate the role of post-approval indications in expanding treatment options towards new cancer types, stages, lines, combinations, and mutations. Heterogeneous clinical development pathways provide insights into potential unintended consequences of IRA-related changes surrounding post-approval research and development.

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来源期刊
Therapeutic innovation & regulatory science
Therapeutic innovation & regulatory science MEDICAL INFORMATICS-PHARMACOLOGY & PHARMACY
CiteScore
3.40
自引率
13.30%
发文量
127
期刊介绍: Therapeutic Innovation & Regulatory Science (TIRS) is the official scientific journal of DIA that strives to advance medical product discovery, development, regulation, and use through the publication of peer-reviewed original and review articles, commentaries, and letters to the editor across the spectrum of converting biomedical science into practical solutions to advance human health. The focus areas of the journal are as follows: Biostatistics Clinical Trials Product Development and Innovation Global Perspectives Policy Regulatory Science Product Safety Special Populations
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