路透社紐約5月15日報道：根據(jù)Gastroenterology雜志四月期發(fā)表的一篇文章，一種新的口服型HCV蛋白酶抑制劑（SCH503034）有很好的耐受性并且可能能夠有效抑制丙型肝炎病毒的1型基因,，這種基因在干擾素治療時很難被破壞,。

    研究者表示，SCH  503034是NS3  蛋白酶的一種特異的抑制劑，而NS3  蛋白酶在丙型肝炎病毒復(fù)制時起到重要作用。德國漢堡薩爾大學(xué)醫(yī)學(xué)院的Christoph  Sarrazin  博士和他的同事們評估了SCH  503034的安全性和耐受性，方法是在未對IFN有反應(yīng),、使用或未使用病毒唑的26名慢性丙型肝炎感染者身上單獨使用SCH  503034或聯(lián)合使用SCH  503034和聚乙二醇修飾的干擾素-α-2b（IFN）。

    作者表示,，不論是單獨使用或與IFN聯(lián)合使用,，SCH  503034  都有很好的耐受性。對單獨或聯(lián)合治療的病毒學(xué)應(yīng)答的評估顯示：SCH  503034和IFN的聯(lián)合作用與那些未對IFN有反應(yīng),、使用或未使用病毒唑的病人的抗HCV活動有關(guān),。研究者補充說明，針對HCV基因型1未應(yīng)答者的二期臨床試驗正在進行中,，目的是為這種潛在的重要治療方法確定最佳劑量和暴露水平,。

    在一篇相關(guān)的社論上，法國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興奮和新奇的，但是,，這些藥物的特殊的抗病毒療效不能用來掩飾它們帶來的新問題,。

    研究結(jié)論是，雖然增加口服HCV抑制劑可以帶來好的療效,，但是對于慢性丙型肝炎的治療來說還可以選擇其它藥物,，包括最佳選擇-聯(lián)合使用聚乙二醇修飾的干擾素-α與病毒唑；所有這些選擇都應(yīng)該再加以研究,，使之能夠在不久的將來給病人帶來益處,。

原始出處:

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