Abivax, a clinical-stage biotechnology company harnessing the immune system to develop novel treatments for inflammatory diseases, viral diseases and cancer, announced today that the first patient was dosed in study ABX464-301, a phase 2a clinical trial of ABX464 to treat patients with moderate to severe active rheumatoid arthritis (RA).The trial has been fully approved in four countries (France, Poland, Czech Republic, and Hungary).ABX464 is an oral once-daily drug candidate with a novel mechanism of action that has already demonstrated positive results in ulcerative colitis (UC), another severe chronic inflammatory disease with closely related biological etiology.
ABX464 was shown to exert its anti-inflammatory effects through a novel mechanism of action;it binds to the cap binding complex (CBC), which essentially sits at the 5’ end of every RNA molecule in the cell.By binding to the CBC, ABX464 reinforces the biological functions of this complex in cellular RNA biogenesis.Specifically, ABX464 enhances the selective splicing of一个长的非编码RNA兴发亚洲唯一官方网站to generate the anti-inflammatory microRNA miR-124, which downregulates pro-inflammatory cytokines and chemokines like TNF-α, Il-6 and MCP-1, thereby putting a brake on inflammation and suggesting broad potential as a novel anti-inflammatory therapeutic agent.
“我们很高兴能够发起患者ABX464的首次临床试验的中度至重度活动性类风湿性关节炎，炎性疾病最大的市场机会。The robust, sustained Phase 2a clinical ulcerative colitis efficacy, demonstrating ABX464’s rapid, potent anti-inflammatory effects, together with ABX464’s broad efficacy in preclinical inflammatory disease models, suggest that ABX464 may have important potential as a novel, highly differentiated anti-inflammatory therapeutic agent,” saidProfessor Hartmut J.Ehrlich, MD, Chief Executive Officer of Abivax。“ABX464的新的作用机制，出版Nature Scientific Reports在2019年一月，说明了这个可口服的分子是如何区分，并提供比市场上销售抗炎药一个行动的潜在互补机制“。
Professor Ehrlich continued：“感谢recent EUR12 million investment由Sofinnova的合作伙伴，我们很感动，按照计划，加速了这种先入级治疗候选人的开发治疗类风湿性关节炎。此外，ABX464的2b期试验治疗溃疡性结肠炎进展顺利，与“第一个病人给予”预计在未来两个星期。此外，我们期待着开始，围绕这个或明年年初结束，ABX464的阶段2a试验治疗克罗恩病。”
ABX464-301 is a phase 2a study designed to evaluate the safety, tolerability and preliminary efficacy of two oral dose-levels of ABX464 administered daily, in combination with methotrexate (MTX), in patients with moderate to severe active RA who had an inadequate response to MTX and/or to one or more anti-tumor necrosis factor alpha (TNFα) biological therapeutics.It is a randomized, double-blind, placebo-controlled, multicenter study in sixty patients with moderate to severe active RA, who will receive 50 mg ABX464, 100 mg ABX464, or placebo during the twelve-week treatment phase.The primary endpoint of the study will be safety and tolerability.Secondary endpoints will include measures of efficacy, such as: change from baseline in the individual components of the American College of Rheumatology (ACR) score;proportion of patients achieving ACR20 response;and, change from baseline in Disease Activity Scores (DAS) in 28 joints.从这个临床试验顶行的数据，预计将在一年左右，到2020年夏季。欲了解更多详情，请点击这里。
Dr.Jean-Marc Steens, Chief Medical Officer of Abivax评论：“类风湿关节炎是一种不可逆的，衰弱和全身自身免疫性疾病，通常需要积极的治疗，以控制。本病代表了数百万受影响的病人，他们的家人和全世界的医疗保健系统的主要负担。处理的标准在过去二十年期间已基本上演变而来，包括现在以及靶向用作第一线常规疾病的抗风湿药物（DMARDs），如甲氨蝶呤，来氟米特，羟氯喹，柳氮磺吡啶，而且生物DMARD（抗TNF） DMARDs (JAK-inhibitors).然而，太多的患者不响应或松动响应这些药物，并用不同的作用机制，如ABX464新的分子，是必要的。