FDA接受阿斯利康naloxegol新药申请

阿斯利康（AstraZeneca）11月19日宣布，FDA已接受naloxegol新药申请（NDA），该药是一种实验性外周作用（peripherally-acting）μ-阿片受体拮抗剂，专门开发用于治疗阿片类药物引发的便秘（opioid-induced constipation，OIC），这是处方阿片类止痛药一种常见的副作用。

naloxegol NDA的提交，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，旨在评价naloxegol治疗OIC的疗效和安全性。其中2个关键性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有望成为首个每日一次的外周作用μ-阿片受体拮抗剂药物，用于OIC患者的治疗。该药是2009年12月阿斯利康与Nektar制药所达成全球独家许可协议的一部分，由Nektar利用其专有的口服小分子聚合物共轭技术开发。根据修订后的许可协议条款，在FDA接受naloxegol NDA后的5个工作日内，阿斯利康将支付7000万美元的里程碑付款。

英文原文：New Drug Application for naloxegol accepted by United States Food and Drug Administration

Tuesday, 19 November 2013

AstraZeneca today announced that the United States Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for naloxegol, an investigational peripherally-acting mu-opioid receptor antagonist (PAMORA), which has been studied in opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, the most common side effect caused by chronic administration of prescription opioid pain medicines.

The NDA filing was based on comprehensive data from the core Phase III KODIAC programme, which is comprised of four clinical trials designed to investigate the safety and efficacy of naloxegol for the treatment of OIC. Two pivotal Phase III studies, KODIAC-04 (n=652) and KODIAC-05 (n=700), both 12-week, multicentre, randomised, double blind, placebo-controlled pivotal trials evaluated 12.5 mg and 25 mg doses of naloxegol, administered once-daily. KODIAC-07, a 12-week safety extension of KODIAC-04, and KODIAC-08 (n= 534) was an open-label controlled, randomised, 52-week, long-term safety trial.

Naloxegol has the potential to be the first once-daily oral PAMORA for patients with OIC in the United States. Naloxegol was developed using Nektar’s oral small molecule polymer conjugate technology.

Naloxegol is part of the exclusive worldwide license agreement announced on 21 September 2009, between AstraZeneca and Nektar Therapeutics. Under the terms of the amended license agreement, AstraZeneca will make a $70 million milestone payment to Nektar within five business days of acceptance of the NDA by the FDA.