Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data.

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-09-23 DOI:10.1007/s12325-025-03368-4

Sandra Santos, Tara M Robinson, David Trueman

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引用次数: 0

Abstract

Introduction: Valoctocogene roxaparvovec is a single administration gene therapy treatment that enables endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. Valoctocogene roxaparvovec is associated with a higher probability of being bleed-free, improvements in annualized bleed rates, and improvements in health-related quality of life compared with FVIII prophylaxis. The economic value of valoctocogene roxaparvovec will be determined, in part, by the duration of time over which the treatment effect is maintained, and the consequences associated with loss of response. Therefore, this analysis aimed to estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating pivotal and longer-term trial data (Phase 3 GENEr8-1 4- to 5-year and a Phase 1/2 study 7-year data) to inform decision-making.

Methods: Using data from the pivotal Phase 3 study GENEr8-1 and longer-term data from the 6E13 vg/kg cohort of Phase 1/2 Study 270-201, time to loss of response was analyzed within a time-to-event analysis framework. Loss of response was defined as a combination of: FVIII level decline < 5% and return to continuous prophylactic treatment and experiencing ≥ 2 treated bleed events in the previous 6 months at the time of return to prophylactic treatment.

Results: Data were available for 134 participants from GENEr8-1, and 7 participants from Study 270-201. The main analysis results for predicted median durability ranged from 11.0 to 17.0 years considering the three statistically best-fitting parametric distributions; considering five plausible distributions, results ranged from 8.1 to 25.6 years. In scenario analyses using different definitions of loss of response, the results were broadly similar, with median durability ranging from 7.2 to 31.8 years.

Conclusion: This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years).

Trial registration number: GENEr8-1: ClinicalTrials.gov identifier, NCT03370913. Study 270-201: ClinicalTrials.gov identifier NCT02576795.

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valoccogene Roxaparvovec治疗男性严重血友病A患者的长期持久性：临床数据的推断。

valoccogene roxaparvovec是一种单给药基因疗法，可使内源性因子VIII （FVIII）产生预防严重血友病a患者出血，与FVIII预防相比，valoccogene roxaparvovec与更高的无出血概率、年化出血率的改善以及与健康相关的生活质量的改善相关。valoccogene roxaparvovec的经济价值将部分取决于维持治疗效果的时间，以及与反应丧失相关的后果。因此，本分析旨在通过推断关键和长期试验数据（3期GENEr8-1 4- 5年和1/2期研究7年数据）来估计valoccogene roxaparvovec治疗效果的长期持久性，从而为决策提供信息。方法：使用关键3期研究GENEr8-1的数据和1/2期研究270-201的6E13 vg/kg队列的长期数据，在时间-事件分析框架内分析反应丧失时间。结果：GENEr8-1中134名参与者和Study 270-201中7名参与者的数据可用。考虑三个统计上最拟合的参数分布，预测中位耐久性的主要分析结果在11.0 ~ 17.0年之间；考虑到五种可能的分布，结果从8.1年到25.6年不等。在使用不同反应丧失定义的情景分析中，结果大致相似，中位持续时间从7.2年到31.8年不等。结论：该分析表明，valoccogene roxaparvovec的潜在治疗益处可能持续超过现有临床试验的随访期，并通过分析的所有参数外推和定义，表明基因治疗可能提供超过先前报道的长期益处（即7年）。试验注册号：GENEr8-1: ClinicalTrials.gov标识符，NCT03370913。研究270-201:ClinicalTrials.gov标识号NCT02576795。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.