Research Division for Development of Anti-Infective Agents, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Japan.
Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
Antiviral Res. 2019 Mar;163:75-81. doi: 10.1016/j.antiviral.2019.01.012. Epub 2019 Jan 23.
Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis.
Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the E model, respectively.
The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C.
These results support that baloxavir marboxil will be effective against a range of virus types/subtypes.
巴洛沙韦（baloxavir）是一种抗病毒药物，可抑制病毒 RNA 转录起始过程中的“帽抢夺”步骤。在 2 期研究中，与安慰剂相比，巴洛沙韦显著缩短了症状缓解时间（TTAS），并显著降低了流感病毒滴度。这提供了其他疗效指标，包括针对不同病毒类型/亚型的疗效和药代动力学/药效学（PK/PD）分析。
对主要和关键次要终点按病毒类型/亚型进行了亚组分析。总共在 2 至 5 个时间点采集了血液样本，包括巴洛沙韦给药后第 2 天。分别使用线性模型和 E 模型对 TTAS 和病毒滴度变化进行 PK/PD 分析。
对于 A/H1N1pdm 病毒患者，每个巴洛沙韦剂量组的中位 TTAS 均明显短于安慰剂组，对于 A/H3N2 和 B 病毒患者，其 TTAS 也短于安慰剂组，但数值上较短。巴洛沙韦在治疗后 1 天内显著降低病毒滴度：对于 A/H1N1pdm、A/H3N2 和 B 病毒，巴洛沙韦 3 种剂量在第 2 天降低病毒滴度的程度均明显大于安慰剂。未发现 TTAS 的明确 PK/PD 关系，但病毒滴度的较大降低与 C 呈正相关。
这些结果支持巴洛沙韦对多种病毒类型/亚型均有效。
