Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, Florida, USA.
Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA.
Pharmacotherapy. 2021 Mar;41(3):315-328. doi: 10.1002/phar.2489. Epub 2021 Feb 17.
To describe the mechanism, efficacy, and safety of novel agents that have reached phase 3 clinical trials for the treatment of biopsy-proven nonalcoholic steatohepatitis (NASH). A literature search was conducted using the PRISMA guidelines of MEDLINE databases (1990 to October 2020) with the following MeSH terms: NASH, nonalcoholic liver disease, fatty liver, liver diseases, steatohepatitis, liver fibrosis; combined with obeticholic acid, FXR agonist, cenicriviroc, CCR5 receptor antagonist, elafibranor, PPAR, selonsertib, ASK-1 inhibitor, resmetirom, THR-β receptor, arachidyl amido cholanoic acid (Aramchol™), and SCD-1 modulator. Results were verified via clinicaltrials.gov, Google Scholar, and Google. Articles were included if the medications of interest had ongoing or completed phase 3 trials in biopsy-proven NASH with outcomes directly related to NASH resolution. Eleven studies were identified involving obeticholic acid (OCA), elafibranor, cenicriviroc, Aramchol, and resmetirom. Two agents have reported data from phase 3 trials: OCA and elafibranor. OCA demonstrated safety and efficacy in NASH with a primary end point of improvement or NASH resolution; a new drug approval has been submitted. Elafibranor failed to show efficacy in NASH in the preliminary report from the RESOLVE-IT trial; however, the study is being extended to reassess outcomes. The remaining agents demonstrated positive results in phase 2b studies and have initiated phase 3 trials. With projections for increased prevalence of patients with NASH and the current lack of treatment options, novel agents with targeted mechanisms could potentially change the treatment landscape. The manufacturer of OCA is first to submit a new drug application for the treatment of NASH. These novel agents may fill a pharmacotherapy gap in patients with NASH and possibly prevent progression to advanced liver disease.
描述已进入非酒精性脂肪性肝炎（NASH）活检证实的 3 期临床试验的新型药物的作用机制、疗效和安全性。使用 PRISMA 指南对 MEDLINE 数据库（1990 年至 2020 年 10 月）进行了文献检索，使用了以下 MeSH 术语：NASH、非酒精性肝病、脂肪肝、肝病、脂肪性肝炎、肝纤维化；与奥贝胆酸、FXR 激动剂、西尼利尤单抗、CCR5 受体拮抗剂、艾拉酚胺、PPAR、塞来昔布、ASK-1 抑制剂、雷西莫特、THR-β 受体、花生四烯酰胺胆碱酸（Aramchol™）和 SCD-1 调节剂。通过 clinicaltrials.gov、Google Scholar 和 Google 验证了结果。如果感兴趣的药物在活检证实的 NASH 中进行了正在进行或已完成的 3 期试验，并且结果与 NASH 缓解直接相关，则纳入了这些试验。确定了 11 项研究，涉及奥贝胆酸（OCA）、艾拉酚胺、西尼利尤单抗、Aramchol 和雷西莫特。有两种药物报告了 3 期试验的数据：OCA 和艾拉酚胺。OCA 在 NASH 中表现出安全性和疗效，主要终点为改善或 NASH 缓解；已提交新药申请。在 RESOLVE-IT 试验的初步报告中，艾拉酚胺未能显示在 NASH 中的疗效；然而，该研究正在延长以重新评估结果。其余药物在 2b 期研究中显示出积极结果，并已启动 3 期试验。随着 NASH 患者的患病率预计增加和目前缺乏治疗选择，具有靶向机制的新型药物可能会改变治疗前景。奥贝胆酸的制造商是第一个提交 NASH 治疗新药申请的制造商。这些新型药物可能会填补 NASH 患者的药物治疗空白，并可能阻止其进展为晚期肝病。
