2014年12月10日讯 /生物谷BIOON/ --阿斯利康（AZN）与合作伙伴Nektar近日宣布，欧盟已批准便秘药物Moventig(naloxegol)用于对通便剂（laxatives）反应不足的成人患者阿片诱导性便秘（OIC）的治疗。Moventig是欧盟批准的首个每日一次的口服外周作用μ-阿片受体拮抗剂（PAMORA）。在美国，Movantik（naloxegol）于2014年9月获FDA批准，是美国首个每日一次口服PAMORA。
阿斯利康与Nektar对naloxegol充满了信心，坚信该药将为双方带来丰厚的回报。有分析师预计，阿片诱导性便秘（OIC）市场到2017年将达到19.8亿美元。尽管主要对手Salix Pharmaceuticals公司类似产品Relistor于今年9月底获FDA批准用于OIC，但该药是一种皮下注射药物。naloxegol具有口服的独特优势，这一特性将使Relistor难以与naloxegol抗衡。但由于阿斯利康与Nektar计划于2015年上半年才将naloxegol推向市场，因此Salix还有一些时间去说服医生和患者使用Relistor治疗OIC。
不过，即便没有Relistor的竞争，阿斯利康也会面对Sucampo公司已上市产品Amitiza的竞争，该药是一种氯离子通道激活剂，于2013年获FDA批准。此外，抗生素巨头Cubist也在销售一种μ-阿片受体拮抗剂Entereg，尽管该药目前尚未收获OIC适应症。但近日美国制药巨头默沙东（Merck & Co）宣布95亿美元收购Cubist，势必会加速开发Entereg的OIC适应症。同时，默沙东拥有强大的商业化网络，在今后必将对阿斯利康在OIC领域的地位形成威胁。
naloxegol III期项目：
Naloxegol的获批，是基于III期KODIAC项目的全面数据，该项目由4个III期临床试验组成，旨在评估naloxegol治疗OIC的疗效和安全性。2个III期研究KODIAC-04和KODIAC-05，是为期12周、多中心、随机、双盲、安慰剂对照、关键性临床试验，评估了每日一次12.5mg和25mg剂量naloxegol。两项试验的主要终点均为治疗12周期间naloxegol相对于安慰剂的OIC响应者比例，次要终点包括首次自发排便（SBM）平均时间等。研究结果表明，这2项研究中，25mg剂量naloxegol均达到了研究的主要终点和次要终点，研究中naloxegol的安全属性与之前的的研究一致。另2个III期试验为KODIAC-07和KODIAC-08，前者为为期12周的KODIAC-04安全性扩展试验，后者为开放标签对照、随机、52周的长期安全性试验。
naloxegol是阿斯利康与Nektar在2009年签署的价值15亿美元全球独家授权协的一部分，该药利用Nektar专有的口服小分子聚合物共轭技术开发。
英文原文：MOVENTIG® approved in the European Union for opioid-induced constipation
First in class treatment approved for adult patients with opioid-induced constipation who have had an inadequate response to laxatives
AstraZeneca today announced that MOVENTIG® (naloxegol) has been granted Marketing Authorisation by the European Commission (EC) for the treatment of opioid-induced constipation (OIC) in adult patients who have had an inadequate response to laxative(s). MOVENTIG is the first once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) to be approved in the European Union (EU).
Opioids play an important role in chronic pain relief and work by binding to mu-receptors in the central nervous system, but they also bind to mu-receptors in the gastrointestinal tract, which can result in patients suffering from OIC.
Briggs Morrison, Executive Vice President, Global Medicines Development & Chief Medical Officer, AstraZeneca, said: “Constipation is one of the most common side effects for those using opioid pain medication. We’re very pleased to have received marketing authorisation for MOVENTIG, as it allows us to offer a new treatment option for the millions of patients across Europe who suffer from opioid-induced constipation and haven’t responded to laxatives.”
The approval of MOVENTIG was based on data from the KODIAC clinical programme, which was comprised of four studies: KODIAC-4, -5, -7 and -8. KODIAC-4 and -5 were both placebo controlled, double-blind, 12 week studies assessing safety and efficacy, while KODIAC-7 was a 12 week safety extension to KODIAC-4, and KODIAC-8 was a 52 week open label, long-term safety study.
The EC marketing authorisation applies to all member states of the EU, Iceland, Norway and Lichtenstein. Today’s announcement follows the approval on 16 September 2014 of MOVANTIKTM (naloxegol) tablets by the US Food and Drug Administration, as the first once-daily PAMORA for the treatment of OIC in adult patients with chronic non-cancer pain.
NOTES TO EDITORS
About MOVENTIG® (naloxegol)
MOVENTIG is a peripherally-acting mu-opioid receptor antagonist (PAMORA) specifically designed for the treatment of opioid-induced constipation (OIC) in adult patients on prescription opioid pain medicines. In Phase III clinical studies, MOVENTIG was administered as a once-daily tablet and was designed to block the binding of opioids to opioid receptors in tissues such as the gastrointestinal (GI) tract.
The KODIAC clinical programme was comprised of four studies: KODIAC-4, -5, -7 and -8. KODIAC-4 and -5 were identically designed, placebo controlled, double-blind, 12 week studies assessing safety and efficacy, while KODIAC-7 was a 12 week safety extension to KODIAC-4, and KODIAC-8 was a 52 week long-term safety study.
MOVENTIG is part of the exclusive worldwide licence agreement announced on 21 September 2009 between AstraZeneca and Nektar Therapeutics. MOVENTIG was developed using Nektar’s oral small molecule polymer conjugate technology.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: