Asselah Tarik, Lampertico Pietro, Aleman Soo, Bourlière Marc, Streinu-Cercel Adrian, Bogomolov Pavel, Morozov Viacheslav, Stepanova Tatiana, Lazar Stefan, Manuilov Dmitry, Mercier Renee-Claude, Tseng Steve, Ye Lei, Flaherty John F, Osinusi Anu, Da Ben L, Chee Grace M, Lau Audrey H, Brunetto Maurizia R, Wedemeyer Heiner
Department of Hepatology, Hôpital Beaujon, Université de Paris-Cité, INSERM UMR1149, Clichy, France.
Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Liver Int. 2025 Apr;45(4):e16174. doi: 10.1111/liv.16174. Epub 2024 Dec 8.
The safety and tolerability of bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, were evaluated in an integrated analysis of clinical trial results from patients with chronic hepatitis delta (CHD).
Week 48 on-treatment clinical and laboratory results from two Phase 2 trials (MYR203 [NCT02888106] and MYR204 [NCT03852433]) and one Phase 3 trial (MYR301 [NCT03852719]) were pooled (N = 269). Patients were grouped as follows: BLV 2 mg (n = 64), BLV 10 mg (n = 115), pegylated interferon-alfa (n = 39) and control (n = 51). The control group consisted of patients assigned to the delayed treatment group in Study MYR301.
Adverse events (AEs) that occurred more frequently with BLV 2 mg and BLV 10 mg versus control included increased total bile acid levels (20% and 17% vs. 0%), injection-site reactions (16% and 20% vs. 0%), headache (16% and 17% vs. 0%), pruritus (11% and 10% vs. 0%) and eosinophilia (9% and 4% vs. 0%). Increases in total bile acid levels were observed with BLV without clear correlation with AEs, such as pruritus, eosinophilia or vitamin D deficiency. Grade 3 or 4 study drug-related AEs occurred in a higher proportion of patients receiving pegylated interferon-alfa (51%) than with BLV 2 or 10 mg (3% and 4%, respectively). There were no serious AEs related to BLV, and no patients discontinued BLV due to an AE. Neither hepatic decompensation nor death occurred.
BLV monotherapy was safe and well tolerated through 48 weeks of treatment in patients with CHD.
NCT02888106, NCT03852433 and NCT03852719.
通过对慢性丁型肝炎（CHD）患者临床试验结果的综合分析，评估新型丁型肝炎病毒进入抑制剂布列韦肽（BLV）的安全性和耐受性。
汇总两项2期试验（MYR203 [NCT02888106]和MYR204 [NCT03852433]）以及一项3期试验（MYR301 [NCT03852719]）第48周的治疗期临床和实验室结果（N = 269）。患者分组如下：BLV 2 mg组（n = 64）、BLV 10 mg组（n = 115）、聚乙二醇化干扰素-α组（n = 39）和对照组（n = 51）。对照组由MYR301研究中分配至延迟治疗组的患者组成。
与对照组相比，BLV 2 mg组和BLV 10 mg组更常出现的不良事件（AE）包括总胆汁酸水平升高（分别为20%和17% vs. 0%）、注射部位反应（16%和20% vs. 0%）、头痛（16%和17% vs. 0%）、瘙痒（11%和10% vs. 0%）和嗜酸性粒细胞增多（9%和4% vs. 0%）。观察到BLV治疗后总胆汁酸水平升高，但与瘙痒、嗜酸性粒细胞增多或维生素D缺乏等AE无明显相关性。接受聚乙二醇化干扰素-α治疗的患者中3级或4级与研究药物相关的AE发生率（51%）高于BLV 2 mg组或10 mg组（分别为3%和4%）。未发生与BLV相关的严重AE，也没有患者因AE而停用BLV。未发生肝失代偿或死亡情况。
在CHD患者中，BLV单药治疗48周的安全性良好且耐受性佳。
NCT02888106、NCT03852433和NCT03852719。
