Department NEUROFARBA, Meyer Children's University Hospital, University of Florence, Florence, Italy.
Birmingham Women's and Children's Hospital, University of Birmingham, Birmingham, UK.
Hepatology. 2022 Aug;76(2):445-455. doi: 10.1002/hep.32393. Epub 2022 Mar 1.
Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic HCV infection. In the USA and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults who previously received an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8-week or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype.
In this Phase 2, multicenter study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients.
All patients (n = 21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21 of 21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults.
The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.
索磷布韦-维帕他韦-伏西瑞韦是一种治疗慢性丙型肝炎病毒（HCV）感染的泛基因型方案。在美国和欧洲，索磷布韦-维帕他韦-伏西瑞韦每日一次，持续 12 周，适用于既往接受过 HCV NS5A 抑制剂治疗的成年人。在欧洲，索磷布韦-维帕他韦-伏西瑞韦也可用于无既往直接作用抗病毒药物（DAA）治疗的情况下，作为 8 周或 12 周的方案。在一项开放标签研究中，我们评估了索磷布韦-维帕他韦-伏西瑞韦在年龄为 12 至 17 岁的慢性 HCV 基因型任意患者中的安全性、疗效和药代动力学。
在这项 2 期、多中心研究中，对于 DAA 初治患者，给予索磷布韦-维帕他韦-伏西瑞韦 400/100/100mg 每日一次，持续 8 周；对于肝硬化或既往 DAA 失败的患者，给予索磷布韦-维帕他韦-伏西瑞韦 12 周治疗。主要疗效终点为治疗后 12 周持续病毒学应答（SVR12）。在第 2 或 4 周时对 14 名患者进行了强化药代动力学采样，并对所有患者采集了群体药代动力学样本。
所有患者（n=21）均为 HCV DAA 初治患者，均无肝硬化。最常见的 HCV 基因型 3a 感染，占 43%。总体而言，100%（21/21）的患者达到了 SVR12。最常见的不良事件是腹痛和头痛（各占 24%）和恶心（19%）；无不良事件导致停药。唯一的严重不良事件，即低血压，被认为与研究药物有关，当天得到缓解，且未中断治疗。索磷布韦-维帕他韦-伏西瑞韦的暴露情况与在成年人中观察到的情况相似。
索磷布韦-维帕他韦-伏西瑞韦的泛基因型方案在治疗青少年慢性 HCV 感染方面具有高度疗效和良好耐受性。
