NEJM:吉利德新药velpatasvir临床三期结果出炉

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据估计，在接下来的十年中由于感染丙肝病毒（HCV）而导致代偿失调性肝硬化患者将会大量增加。长久以来，代偿失调性肝硬化患者的唯一的治疗选择就是接受肝脏移植手术。近来，新近获批的直接抗病毒药物的临床研究表明其可以安全有效地治疗患有代偿失调性肝硬化病人的HCV感染，这一成功的治疗是和早期提升肝功能有关。目前唯一的批准的治疗代偿失调性肝硬化患者的HCV的处方是ledipasvir–sofosbuvir加利巴韦林，疗程为24周。这已经在欧洲杯批准用于治疗HCV基因型1和4。

研究人员公布了吉利德公司的新药velpatasvir联用sofosbuvir治疗代偿失调性肝硬化患者的HCV感染的临床三期结果。在此次三期、非盲临床试验包括的HCV基因型1-6的患者。这些患者有的曾接受过治疗，有的未曾接受过治疗，但均患有代偿失调性肝硬化。患者被随机均分为三组。第一组患者接受核苷酸聚合酶抑制剂sofosbuvir和NS5A抑制剂velpatasvir治疗，每周一次，持续12周；第二组则是sofosbuvir-velpatasvir加上利巴韦林进行治疗，也是持续12周的治疗；第三组则是sofosbuvir-velpatasvir治疗24周。主要终点是在治疗结束后12周的持续性病毒响应。共有267名患者参与此次试验。六种基因型依次为78%、4%、15%、3%、0以及低于1%。持续性病毒响应的总体比例为83%。三组的持续性病毒响应比例没有显著性差异。

此次研究表明，sofosbuvir–velpatasvir无论是否联用利巴韦林治疗12周以及sofosbuvir–velpatasvir治疗24周都可以达到很高的持续性病毒响应比例。

来源：MedSci

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Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis

Michael P. Curry, M.D., Jacqueline G. O’Leary, M.D., M.P.H., Natalie Bzowej, M.D., Andrew J. Muir, M.D., Kevin M. Korenblat, M.D., Jonathan M. Fenkel, M.D., K. Rajender Reddy, M.D., Eric Lawitz, M.D., Steven L. Flamm, M.D., Thomas Schiano, M.D., Lewis Teperman, M.D., Robert Fontana, M.D., Eugene Schiff, M.D., Michael Fried, M.D., Brian Doehle, Ph.D., Di An, Ph.D., John McNally, Ph.D., Anu Osinusi, M.D., Diana M. Brainard, M.D., John G. McHutchison, M.D., Robert S. Brown, Jr., M.D., M.P.H., and Michael Charlton, M.D.

BACKGROUND
As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.

METHODS
We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child–Pugh–Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir–velpatasvir plus ribavirin for 12 weeks, or sofosbuvir–velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.

RESULTS
Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir–velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir–velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir–velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir–velpatasvir, 16% of those who received 12 weeks of sofosbuvir–velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir–velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin.

CONCLUSIONS
Treatment with sofosbuvir–velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir–velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis.

http://www.nejm.org/doi/full/10. ... =featured_home&