2014年12月10日讯 /生物谷BIOON/ --礼来和合作伙伴Incyte近日公布了类风湿性关节炎（RA）药物baricitinib关键III期RA-BEACON研究的积极顶线数据。
该研究在527例既往经至少一种抗肿瘤坏死因子（TNF）制剂（包括重磅药物阿达木单抗Humira和依那西普Enbrel）治疗失败正服用稳定剂量常规疾病修饰抗风湿药物（cDMARD）的中度至重度类风湿性关节炎（RA）患者中开展。
研究中，除了接受cDMARDs背景疗法外，患者还接受每日一次baricitinib或安慰剂治疗。研究结果表明，治疗12周后，与安慰剂相比，baricitinib达到了改善ACR20反应的主要终点。安全性方面，baricitinib的副作用与安慰剂相似，常见的不良反应包括头痛，上呼吸道感染和鼻咽炎。RA-BEACON研究是baricitinib III期项目的首个关键研究。礼来将于2015年在科学会议上公布数个关键III期试验的数据。。
抗肿瘤坏死因子（TNF）疗法如修美乐Humira（阿达木单抗）、类克Remicade（英夫利西单抗）美罗华Rituxan/MabThera（利妥昔单抗）、恩利Enbrel（依那西普）是全球最畅销的药物，这4种均位列《2013年最畅销的25个药物》榜单。而RA-BEACON研究的成功，预示着baricitinib有望在本已拥挤不堪的市场中开辟一块天地。
目前，礼来和Incyte正在开展一项大型III期项目，包括在美国开展的4个研究和在中国开展的1个研究，涉及3000例类风湿性关节炎（RA）患者，评估baricitinib的疗效及安全性。礼来预计将于2015年底完成美国的4个III期研究，并根据结果向FDA提交baricitinib的上市申请。
与常规的注射型TNF阻断剂不同，礼来的baricitinib是一种口服JAK抑制剂，旨在阻断炎症信号和治疗免疫学疾病（包括类风湿性关节炎）的根本病因。辉瑞的口服JAK抑制剂Xeljan于2012年获批上市，业界曾对该药寄予厚望，但上市之后却并没有如预期的很快达到行业预期，导致JAK抑制剂的前景暗淡不少；近日，巨头强生宣布终止与安斯泰来近10亿美元的合作，该项合作中同样涉及一种JAK抑制剂ASP015K，这一变故也多少给JAK抑制剂的前景带来了一些动荡。
英文原文：Lilly and Incyte's oral arthritis drug aces its first Phase III test
A new rheumatoid arthritis pill from Eli Lilly ($LLY) and Incyte ($INCY) beat out placebo in a pivotal trial, the first late-stage success for a drug the companies hope can carve out a space in a crowded market.
In a Phase III trial on 527 RA patients who failed on TNF inhibitors like Enbrel and Humira, Lilly and Incyte's baricitinib met its main goal of significantly improving disease score compared to placebo. On the safety side, baricitinib's side effect profile was similar to placebo, the companies said, with common adverse events including headache, upper respiratory tract infection and nasopharyngitis. The partners are releasing only top-line results for now, planning to divulge full data at a scientific meeting next year.
The success allows Lilly and Incyte to check the first box in their 3,000-patient late-stage program, which includes four ongoing trials in the U.S. and one in China. The two expect to complete the first four studies by the end of 2015, mapping a path to regulators from there.
"People with rheumatoid arthritis who have had an inadequate response to TNF inhibitors are generally considered to be the least responsive to subsequent treatments," Lilly Senior Vice President David Ricks said in a statement. "These results give us further confidence in the potential for baricitinib to be a meaningful treatment option for those suffering from this debilitating condition."
And unlike the injected TNF blockers that have brought in billions for AbbVie ($ABBV) and Amgen ($AMGN), baricitinib is an oral JAK inhibitor designed to block inflammatory signaling and treat the underlying cause of immune diseases including RA, all without the need for needles.
Meanwhile, JAK inhibitors for inflammatory disease have lost some of their luster of late, as Pfizer's ($PFE) Xeljanz has failed to catch on as quickly as analysts expected when it won approval in 2012, and Johnson & Johnson ($JNJ) has walked away from a nearly $1 billion deal with Astellas covering a similar treatment called ASP015K.