Abstract：
OBJECTIVE: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
METHODS: In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA.
RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV.
CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96.
UNASSIGNED: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96.
RESULTS:
UNASSIGNED: NCT03852719.
METHODS: In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA.
RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV.
CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96.
UNASSIGNED: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96.
RESULTS:
UNASSIGNED: NCT03852719.
摘要：
目标：丁维肽（BLV），一流的进入抑制剂，在欧洲被批准用于治疗慢性丁型肝炎（CHD）。BLV单药治疗优于延迟治疗（W）48周，主要疗效终点，在MYR301研究（NCT03852719）中。这里,我们评估了在W96之前继续BLV治疗是否会改善病毒学和生化应答率，特别是在W24时未达到病毒学应答的患者中.
方法：在此过程中，开放标签，随机3期研究，CHD患者（N=150）随机（1：1：1）接受BLV2（n=49）或10mg/天（n=50）治疗，每个144周，或延迟治疗48周，然后BLV10mg/天，持续96周（n=51）。联合反应被定义为检测不到丁型肝炎病毒（HDV）RNA或HDVRNA减少≥2log10IU/mL从基线和丙氨酸转氨酶（ALT）正常化。其他终点包括病毒学应答，ALT正常化,和HDVRNA的变化。
结果：在150名患者中，143（95%）完成了96周的研讨。W48和W96之间的疗效反应得到维持和/或改善，相似的组合，病毒学,生化反应率在BLV2和10mg之间。在W24时具有次优的早期病毒学应答的患者中,43%的无应答者和82%的部分应答者在W96时实现病毒学应答。生化改善通常与病毒学反应无关。不良事件（AE）大多为轻度，无与BLV相关的严重不良事件。
结论：长期BLV治疗可维持和/或增加病毒学和生化反应，包括那些早期病毒学应答欠佳的患者。通过W96，BLV单药治疗冠心病是安全且耐受性良好的。
■根据长达48周治疗的临床研究结果，2023年7月，丁维肽被完全批准用于欧洲慢性丁型肝炎（CHD）的治疗。从长远来看，了解bulevirtide的疗效和安全性对医疗保健提供者很重要。在这个分析中,我们证明,在CHD患者中,bulevirtide单药治疗96周与联合治疗的持续改善相关,病毒学,和生化反应以及肝脏僵硬度从第48周在2-mg和10-mg的剂量。在第24周时对bulevirtide的病毒学反应欠佳的患者也受益于持续治疗，大多数人在第96周达到病毒学应答或生化改善。
结果：
■NCT03852719。
方法：在此过程中，开放标签，随机3期研究，CHD患者（N=150）随机（1：1：1）接受BLV2（n=49）或10mg/天（n=50）治疗，每个144周，或延迟治疗48周，然后BLV10mg/天，持续96周（n=51）。联合反应被定义为检测不到丁型肝炎病毒（HDV）RNA或HDVRNA减少≥2log10IU/mL从基线和丙氨酸转氨酶（ALT）正常化。其他终点包括病毒学应答，ALT正常化,和HDVRNA的变化。
结果：在150名患者中，143（95%）完成了96周的研讨。W48和W96之间的疗效反应得到维持和/或改善，相似的组合，病毒学,生化反应率在BLV2和10mg之间。在W24时具有次优的早期病毒学应答的患者中,43%的无应答者和82%的部分应答者在W96时实现病毒学应答。生化改善通常与病毒学反应无关。不良事件（AE）大多为轻度，无与BLV相关的严重不良事件。
结论：长期BLV治疗可维持和/或增加病毒学和生化反应，包括那些早期病毒学应答欠佳的患者。通过W96，BLV单药治疗冠心病是安全且耐受性良好的。
■根据长达48周治疗的临床研究结果，2023年7月，丁维肽被完全批准用于欧洲慢性丁型肝炎（CHD）的治疗。从长远来看，了解bulevirtide的疗效和安全性对医疗保健提供者很重要。在这个分析中,我们证明,在CHD患者中,bulevirtide单药治疗96周与联合治疗的持续改善相关,病毒学,和生化反应以及肝脏僵硬度从第48周在2-mg和10-mg的剂量。在第24周时对bulevirtide的病毒学反应欠佳的患者也受益于持续治疗，大多数人在第96周达到病毒学应答或生化改善。
结果：
■NCT03852719。
