Comparative Effectiveness of Valoctocogene Roxaparvovec and Efanesoctocog Alfa in the Treatment of Severe Hemophilia A: A Matching-Adjusted Indirect Comparison of Bleeding Frequency.
Thomas G Douglas, Sandra Santos, David R Hinds, Anthony J Hatswell, Kurt Taylor
{"title":"Comparative Effectiveness of Valoctocogene Roxaparvovec and Efanesoctocog Alfa in the Treatment of Severe Hemophilia A: A Matching-Adjusted Indirect Comparison of Bleeding Frequency.","authors":"Thomas G Douglas, Sandra Santos, David R Hinds, Anthony J Hatswell, Kurt Taylor","doi":"10.1007/s12325-025-03339-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Hemophilia A, an X-linked recessive bleeding disorder, is characterized by reduced factor VIII (FVIII) activity. Hemophilia A can significantly impact a person's quality of life because of the risk of spontaneous bleeding. Treatment for hemophilia A aims to prevent bleeding from occurring. The innovation of gene therapies for use in hemophilia has the potential to replace prophylaxis treatment by enabling a single treatment infusion that sustains endogenous FVIII production for years. This analysis assessed the comparative effectiveness of valoctocogene roxaparvovec, a gene therapy, versus prophylactic FVIII replacement therapy with efanesoctocog alfa, given the current lack of comparative evidence between these treatments.</p><p><strong>Methods: </strong>Comparison between valoctocogene roxaparvovec and efanesoctocog alfa was conducted using matching-adjusted indirect comparison (MAIC). Patient-level data from the phase III GENEr8-1 trial of valoctocogene roxaparvovec were reweighted to align with baseline characteristics of aggregate-level data from XTEND-1, a phase III trial of efanesoctocog alfa. Matching variables included proportion of patients with zero treated bleeds and mean annualized bleed rate (ABR) for treated bleeds prior to initiating therapy. Following reweighting, the proportion of patients who had experienced zero bleeds after 52 weeks was compared, along with mean ABR-each population was assessed for treated bleeds, treated joint bleeds, and treated spontaneous bleeds.</p><p><strong>Results: </strong>Following MAIC weighting, patients treated with valoctocogene roxaparvovec had higher odds of experiencing zero treated bleeds (OR 2.68, 95% CI 1.18-6.14) and zero treated joint bleeds (OR 2.75, 95% CI 1.09-6.86) compared with efanesoctocog alfa. Odds of zero treated spontaneous bleeds were also higher for valoctocogene roxaparvovec, but not statistically significant. Mean ABRs for treated bleeds, treated joint bleeds, and treated spontaneous bleeds were similar between groups, with no statistically significant differences.</p><p><strong>Conclusion: </strong>This MAIC suggests that valoctocogene roxaparvovec provides a greater likelihood of patients experiencing zero treated bleeds compared with efanesoctocog alfa during the first year following treatment initiation.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12325-025-03339-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Hemophilia A, an X-linked recessive bleeding disorder, is characterized by reduced factor VIII (FVIII) activity. Hemophilia A can significantly impact a person's quality of life because of the risk of spontaneous bleeding. Treatment for hemophilia A aims to prevent bleeding from occurring. The innovation of gene therapies for use in hemophilia has the potential to replace prophylaxis treatment by enabling a single treatment infusion that sustains endogenous FVIII production for years. This analysis assessed the comparative effectiveness of valoctocogene roxaparvovec, a gene therapy, versus prophylactic FVIII replacement therapy with efanesoctocog alfa, given the current lack of comparative evidence between these treatments.
Methods: Comparison between valoctocogene roxaparvovec and efanesoctocog alfa was conducted using matching-adjusted indirect comparison (MAIC). Patient-level data from the phase III GENEr8-1 trial of valoctocogene roxaparvovec were reweighted to align with baseline characteristics of aggregate-level data from XTEND-1, a phase III trial of efanesoctocog alfa. Matching variables included proportion of patients with zero treated bleeds and mean annualized bleed rate (ABR) for treated bleeds prior to initiating therapy. Following reweighting, the proportion of patients who had experienced zero bleeds after 52 weeks was compared, along with mean ABR-each population was assessed for treated bleeds, treated joint bleeds, and treated spontaneous bleeds.
Results: Following MAIC weighting, patients treated with valoctocogene roxaparvovec had higher odds of experiencing zero treated bleeds (OR 2.68, 95% CI 1.18-6.14) and zero treated joint bleeds (OR 2.75, 95% CI 1.09-6.86) compared with efanesoctocog alfa. Odds of zero treated spontaneous bleeds were also higher for valoctocogene roxaparvovec, but not statistically significant. Mean ABRs for treated bleeds, treated joint bleeds, and treated spontaneous bleeds were similar between groups, with no statistically significant differences.
Conclusion: This MAIC suggests that valoctocogene roxaparvovec provides a greater likelihood of patients experiencing zero treated bleeds compared with efanesoctocog alfa during the first year following treatment initiation.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
