路透社纽约5月15日报道：根据Gastroenterology杂志四月期发表的一篇文章，一种新的口服型HCV蛋白酶抑制剂（SCH503034）有很好的耐受性并且可能能够有效抑制丙型肝炎病毒的1型基因，这种基因在干扰素治疗时很难被破坏。
研究者表示，SCH 503034是NS3 蛋白酶的一种特异的抑制剂，而NS3 蛋白酶在丙型肝炎病毒复制时起到重要作用。德国汉堡萨尔大学医学院的Christoph Sarrazin 博士和他的同事们评估了SCH 503034的安全性和耐受性，方法是在未对IFN有反应、使用或未使用病毒唑的26名慢性丙型肝炎感染者身上单独使用SCH 503034或联合使用SCH 503034和聚乙二醇修饰的干扰素-α-2b（IFN）。
作者表示，不论是单独使用或与IFN联合使用，SCH 503034 都有很好的耐受性。对单独或联合治疗的病毒学应答的评估显示：SCH 503034和IFN的联合作用与那些未对IFN有反应、使用或未使用病毒唑的病人的抗HCV活动有关。研究者补充说明，针对HCV基因型1未应答者的二期临床试验正在进行中，目的是为这种潜在的重要治疗方法确定最佳剂量和暴露水平。
在一篇相关的社论上，法国Creteil ，Hopital Henri Mondor的Jean-Michel Pawlotsky博士表示，新型的口服抗病毒方法是令人兴奋和新奇的，但是，这些药物的特殊的抗病毒疗效不能用来掩饰它们带来的新问题。
研究结论是，虽然增加口服HCV抑制剂可以带来好的疗效，但是对于慢性丙型肝炎的治疗来说还可以选择其它药物，包括最佳选择-联合使用聚乙二醇修饰的干扰素-α与病毒唑；所有这些选择都应该再加以研究，使之能够在不久的将来给病人带来益处。
原始出处:
Gastroenterology ，Volume 132, Issue 4, Pages 1270-1278 (April 2007)
SCH 503034, a Novel Hepatitis C Virus Protease Inhibitor, Plus Pegylated Interferon α-2b for Genotype 1 Nonresponders
Christoph Sarrazin⁎#, Regine Rouzier‡, Frank Wagner§, Nicole Forestier⁎#, Dominique Larrey∥, Samir K. Gupta¶, Musaddeq Hussain¶, Amrik Shah¶1, David Cutler¶, Jenny Zhang¶2, Stefan Zeuzem⁎#
Received 30 August 2006; accepted 14 December 2006 published online 26 January 2007.
Background & Aims: SCH 503034 is a novel and potent oral hepatitis C virus (HCV) protease inhibitor. In this phase Ib study, we assessed safety parameters and virologic response of combination of SCH 503034 plus pegylated (PEG) interferon (IFN) α-2b in patients with HCV genotype 1 infections who were previously nonresponders to PEG-IFN-α-2b ± ribavirin therapy. Methods: This was a multicenter, open-label, 2-dose level, 3-way crossover, randomized (to crossover sequence) study carried out in 3 medical centers in Europe. Adult patients received SCH 503034 200 mg (n = 14) or 400 mg (n = 12) 3 times daily orally and PEG-IFN-α-2b 1.5 μg/kg subcutaneously once each week. Patients received SCH 503034 as monotherapy for 1 week, PEG-IFN-α-2b as monotherapy for 2 weeks, and combination therapy for 2 weeks with washout periods between each treatment period. Results: Combination therapy with SCH 503034 and PEG-IFN-α-2b was well tolerated, with no clinically significant changes in safety parameters. Mean maximum log10 changes in HCV RNA were −2.45 ± 0.22 and −2.88 ± 0.22 for PEG-IFN-α-2b plus 200 mg and 400 mg SCH 503034, respectively, compared with −1.08 ± 0.22 and −1.61 ± 0.21 for SCH 503034 200 mg and 400 mg, respectively, and −1.08 ± 0.22 and −1.26 ± 0.20 for PEG-IFN-α-2b alone in the 200 mg and 400 mg SCH 503034 groups, respectively. Conclusions: SCH 503034 plus PEG-IFN-α-2b was well tolerated in patients with HCV genotype 1 nonresponders to PEG-IFN-α-2b ± ribavirin. These preliminary results of antiviral activity of the combination suggest a potential new therapeutic option for this hard-to-treat, nonresponder patient population.
Abbreviations used in this paper: AUC, area under the plasma concentration-time curve, IFN, interferon, PEG, pegylated, RT-PCR, reverse-transcriptase polymerase chain reaction, TRIF, toll-interleukin-1 receptor-domain-containing adaptor inducing IFN-ß
Department of Internal Medicine II, Saarland University Hospital, Homburg, Germany
‡ Centre Cap, Montpellier, France
§ Charité Research Organisation, Charité Universitätsmedizin, Berlin, Germany
∥ Service d’Hépatogastro-Entérologie et Transplantation, Montpellier School of Medicine, and INSERM Unit 632, Montpellier, France
¶ Schering-Plough Research Institute, Kenilworth, New Jersey
# Department of Internal Medicine I, J.W. Goethe-University Hospital, Frankfurt am Main, Germany
Address requests for reprints to: Stefan Zeuzem, MD, Professor of Medicine, J.W. Goethe-University Hospital, Medizinische Klinik I, 60590 Frankfurt am Main, Germany. fax: (49) 069-6301-6448.
This study was carried out by Schering-Plough Research Institute as part of the clinical development program for SCH 503034.
1 A.S.’s present affiliation is Johnson & Johnson, Raritan, New Jersey.
2 J.Z.’s present affiliation is Bristol-Myers Squibb, Princeton, New Jersey.
PII: S0016-5085(07)00180-1
doi:10.1053/j.gastro.2007.01.041
© 2007 AGA Institute. Published by Elsevier Inc. All rights reserved.
2007;132:1270-1278,1611-1615
