治療C型肝炎的新選項：Ropeginterferon alfa-2b (P1101)

An Alternative Treatment for Hepatitis C: Ropeginterferon alfa-2b (P1101)

在臺灣20歲以上的成年人高達4.4%感染C型肝炎病毒（HCV），而且大部分的病患都未接受治療。目前雖然口服直接抗病毒藥物（DAAs）已獲臺灣衛生福利部食品藥物管理署（TFDA）的核准使用於C型肝炎，但早期因為價格昂貴也尚未全面納入全民健康保險（NHI）給付，今年以前在臺灣的臨床應用上，還是以二線治療使用為主。Ropeginterferon alfa-2b（P1101）是一創新的聚乙二醇化之干擾素α-2b。利用獨特的PEGylation耦合技術，將40 kDa的聚乙二醇分子鍵結在特定地脯氨酸修飾干擾素的N-端位置，並主要形成單一成份的位置異構物，製造出目前世界上最純的長效型干擾素。在一個執行於健康志願者的第一期臨床試驗和兩個慢性C型肝炎患者的第二期臨床試驗中，P1101與其它長效型干擾素相比，其藥物動力學特性和作用持續的時間更長。每雙週施打P1101 360μg併用雷巴威林治療組，對慢性C型肝炎病毒基因型第2型病患可達約90%的持續病毒反應（SVR），而對慢性C型肝炎病毒基因型第1型病患每週施打P1101 270μg併用雷巴威林的結果亦可達到80%的SVR。治療期間超過90%的不良事件（TEAE）為1級或2級（通用術語標準不良事件，CTCAE）。於慢性C型肝炎病毒基因型第1型病患治療結果中，P1101併用雷巴威林治療的患者憂鬱和類流感症狀，少於採用其他長效型干擾素併用雷巴威林的患者。從治療真性紅血球增生症的關鍵性第三期臨床試驗研究中也顯示出高耐受性。因此，P1101是有別於目前長效型干擾素的新選擇，提供慢性C型肝炎病患更方便的療程（每雙週施打一針v.s每週施打一針），並具有相同的療效及更佳的耐受性。

In Taiwan, the prevalence of hepatitis C virus (HCV) infection among adults aged over 20 years old is high (4.4%), but the majority of them do not get treatment. Although direct antiviral agents (DAAs) are approved by Taiwan Food and Drug Administration (TFDA), they are still expensive and mostly used as second line in clinical practice, and are not fully reimbursed by the national health insurance (NHI). Ropeginterferon alfa-2b (P1101) is a novel pegylated proline-interferon alfa-2b with a 40 kDa branched polyethylene glycol chain conjugated predominantly at its N-terminus with one major positional isomer, resulting in the purest pegylated interferon in the world. In a phase 1 study for healthy volunteers and two phase 2 studies for CHC, P1101 had demonstrated better pharmacokinetic profile and longer duration of action than peginterferon alfa-2a. P1101 360 μg q2w + RBV has yielded about 90% sustained virological response (SVR) rate for CHC genotype 2 and P1101 270μg q1w + RBV has yielded 80% SVR rate for CHC genotype 1. Over 90% of treatment emergent adverse events (TEAEs) were grade 1 or 2(common terminology criteria for adverse events, CTCAE). Depression and flu-like symptoms were fewer in patients treated with P1101 + RBV than in those treated with peginterferon alfa-2a + RBV for CHC genotype 1. High tolerability was also shown in a pivotal phase 3 study in treating polycythemia vera. P1101 is therefore an alternative of long-acting interferon with comparable efficacy, better tolerability and more convenient dosing schedule (every-2-week, q2w vs. weekly, q1w) for treating CHC.