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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EChronic hepatitis B virus (HBV) infection is rarely cured with current therapies, and there is no effective therapy for hepatitis D virus (HBD) coinfection. Myrcludex B is a first-in-class entry inhibitor that inactivates the HBV and HDV receptor sodium taurocholate cotransporting polypeptide. This article discusses a phase 2a study evaluating the safety, tolerability, and antiviral efficacy of Myrcludex B.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHepatology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELiver Conditions\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EViral Infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EChronic hepatitis B virus (HBV) infection is rarely cured with current therapies, and there is no effective therapy for hepatitis D virus (HBD) coinfection. Myrcludex B is a first-in-class entry inhibitor that inactivates the HBV and HDV receptor sodium taurocholate cotransporting polypeptide (NTCP). Myrcludex B specifically targets NTCP at the hepatocyte surface, inhibiting HBV and HDV receptor function and NTCP-mediated bile salt uptake into hepatocytes. Phase 1 clinical trials have demonstrated the safety of Myrcludex B.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe objective of the phase 2a study, presented by Stephan Urban, MD, University Hospital Heidelberg, Heidelberg, Germany, was to evaluate the safety, tolerability, and antiviral efficacy of Myrcludex B. The study included 2 cohorts. Cohort A consisted of 40 hepatitis B e antigen-negative patients with chronic HBV infection, HBV DNA \u0026gt; 2000 IU\/mL, median HBV DNA 4.7 log\u003Csub\u003E10\u003C\/sub\u003E IU\/ mL, and no cirrhosis. These patients were treated for 12 weeks with once-daily subcutaneous Myrcludex B at 0.5 mg, 1 mg, 2 mg, 5 mg, or 10 mg doses (n = 8\/dosage group). Treatment was extended to 24 weeks for patients in the 10 mg group. Cohort B included 24 patients with HDV and compensated liver disease scheduled for 48 weeks of pegylated interferon-alpha (PEG-IFN\u03b1) therapy. Eight patients were pretreated with Myrcludex B 2 mg alone for 24 weeks (Cohort B1). Eight patients were treated with PEG-IFN\u03b1 plus Myrcludex B for the first 24 weeks (Cohort B2), and the 8 remaining patients were treated with PEG-IFN\u03b1 alone (Cohort B3). The end points for both cohorts were biochemical and virologic response, immunogenicity, bile salt elevations, pharmacokinetics, and safety and tolerability.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EHBV DNA levels declined during Myrcludex B treatment in all groups. A pronounced effect of \u0026gt; 1 log\u003Csub\u003E10\u003C\/sub\u003E HBV reduction occurred in 6 patients in the 10 mg dose group and in 7 patients in the lower-dosing groups.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EMyrcludex B had no significant effect on hepatitis B surface antigen (HBsAg) serum levels during treatment. At week 24, a \u0026gt; 1 log\u003Csub\u003E10\u003C\/sub\u003E HDV RNA reduction occurred in 6 Cohort B1 patients during Myrcludex B monotherapy and 7 Cohort B2 patients during combination therapy. HDV RNA became negative in 2 patients during Myrcludex B monotherapy and in 5 patients receiving combination therapy. Myrcludex B induced preS-specific antibodies in 4 patients during Myrcludex monotherapy and in 7 patients during combination therapy.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ETreatment with Myrcludex B normalized alanine aminotransferase (ALT) levels in 55% of patients; median ALT levels declined from 76 U\/L to 36 U\/L at week 12 (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001). Myrcludex B had a dose-dependent effect on serum bile salt levels. Rapid elevation of taurocholic acid and glyocholic acid were observed with Myrcludex B \u0026gt; 1 mg\/day. Myrcludex B withdrawal resulted in rapid bile salt normalization.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EAdverse events included injection-site dermatitis (n = 3, 10 mg group) and psoriasis exacerbation leading to discontinuation (n = 1, Cohort B2).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe investigators concluded that Myrcludex B was safe and well tolerated in HBsAg-positive patients with or without HDV coinfection. HBV entry inhibition was associated with HBV DNA and strong HDV RNA declines and improved biochemical disease activity.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/48\/19.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzofs2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}