阿斯利康$12.6亿痛风药物lesinurad提交欧盟审查

英国制药巨头阿斯利康（AstraZeneca）近日宣布，欧洲药品管理局（EMA）已接受审查痛风药物lesinurad（200mg片剂）的上市许可申请（MAA）。lesinurad是一种选择性尿酸再吸收抑制剂（SURI），能够抑制URAT1转运体增加尿酸排泄从而降低血尿酸（sUA）。目前，阿斯利康正开发lesinurad联合黄嘌呤氧化酶（XO）抑制剂（别嘌呤醇或非布索坦）用于痛风患者高尿酸血症（hyperuricaemia）的治疗。

lesinurad由阿斯利康于2012年耗资12.6亿美元收购Ardea公司获得，并对该药寄予厚望，期望能帮助在不断增长的全球痛风市场中攫取更大的市场份额。当前，市面上流行的痛风药物主要是使用了长达50年之久的别嘌呤醇（allopurinol）和5年前上市的非不索坦（febuxostat），但这2种药物并不适用于所有痛风患者。因此，市场急需新的痛风药物。根据2014年8月公布的消息，lesinurad在III期项目大获成功，为该药的监管批准提供了保障。有分析师预计，lesinurad一旦上市，其销售额将突破10亿美元，并为阿斯利康带来重磅回报。

lesinurad MAA的提交，是基于关键III期项目（CLEAR1，CLEAR2，CRYSTAL）的积极数据。CLEAR1和CLEAR2研究调查了lesinurad（200mg和400mg，每天一次）与黄嘌呤氧化酶（XO）抑制剂别嘌呤醇（allopurinol）组合疗法，用于当前别嘌呤醇剂量未实现目标sUA水平的有症状痛风患者的治疗。数据显示，200mg剂量和400mg剂量lesinurad + 别嘌呤醇组合疗法均达到了研究的主要终点，在治疗的6个月时，与别嘌呤醇单药治疗组相比，2个联合治疗组有显著更高比例的患者实现sUA＜6.0mg/dL的目标，数据具有统计学显著差异（p＜0.0001）。

CRYSTAL研究调查了lesinurad（200mg和400mg，每天一次）与黄嘌呤氧化酶（XO）抑制剂非布索坦（febuxostat，800mg，每天一次）组合疗法，用于伴有痛风石（tophi，即关节和皮肤中沉积有可见的尿酸晶体结节）的痛风患者中开展。数据显示，400mg剂量lesinurad＋非不索坦组合疗法达到了研究的主要终点，在治疗的6个月时，与非不索坦单药治疗组相比，联合治疗组
有显著更高比例的患者实现sUA＜5.0mg/dL的目标，数据具有统计学显著差异（p＜0.0001）。

这些数据表明，lesinurad与黄嘌呤氧化酶（XO）抑制剂（别嘌呤醇/非布索坦）的组合疗法，有望为广大痛风患者提供潜在的新治疗选择。

英文原文：Marketing Authorisation Application for gout treatment lesinurad accepted by European Medicines Agency

Thursday, 22 January 2015

AstraZeneca today announced the European Medicines Agency has accepted the Marketing Authorisation Application (MAA) for lesinurad 200mg tablets. Lesinurad is a selective uric acid reabsorption inhibitor (SURI) developed for the chronic treatment of hyperuricaemia in combination with xanthine oxidase (XO) inhibitors allopurinol or febuxostat in gout patients when additional therapy is warranted.

The MAA filing was based on data from the CLEAR1, CLEAR2 and CRYSTAL pivotal Phase III combination therapy studies. CLEAR1 and CLEAR2 were 12-month, multicentre, randomised, placebo-controlled studies that evaluated the efficacy and safety of a once daily dose of lesinurad in combination with allopurinol versus allopurinol alone, in symptomatic gout patients not achieving target serum uric acid (sUA) levels on their current allopurinol therapy. CRYSTAL was a 12-month, multicentre, randomised, placebo-controlled study that evaluated the efficacy and safety of a once daily dose of lesinurad in combination with febuxostat compared to febuxostat alone in gout patients with tophi (deposits of uric acid crystals in joints and skin).

Between 40 to 80% of patients do not achieve recommended sUA goals with the current standard of care of an XO inhibitor alone. XO inhibitors including allopurinol and febuxostat reduce the production of uric acid. Lesinurad works by inhibiting the uric acid transporter URAT1 in the kidney, thereby increasing uric acid excretion resulting in lower sUA. Combination therapy with lesinurad and an XO inhibitor provides a dual mechanism approach targeting both excretion and production of uric acid which effectively lowers sUA and enables significantly more patients to achieve and maintain target treatment goals to control their disease.

The CLEAR1, CLEAR2 and CRYSTAL studies were conducted by Ardea Biosciences, a member of the AstraZeneca Group.

NOTES TO EDITORS

About Lesinurad

Lesinurad is a selective uric acid reabsorption inhibitor (SURI) that inhibits the URAT1 transporter and is being studied as an investigational agent for the treatment of gout. URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen. By inhibiting URAT1, lesinurad increases uric acid excretion and thereby lowers sUA. Lesinurad also inhibits OAT4, a uric acid transporter involved in diuretic-induced hyperuricaemia.

About Gout

Gout is a serious, chronic and debilitating form of inflammatory arthritis. There are more than 15.8 million diagnosed cases of gout in major markets. Gout is caused by a metabolic disorder, hyperuricaemia (elevated sUA), which leads to the deposition of crystals in musculoskeletal structures including joints, in the kidneys, and in other tissues.

About Ardea Biosciences

Ardea Biosciences, Inc. was acquired by AstraZeneca in June 2012. It is located in San Diego, California and is a member of the AstraZeneca Group. Ardea is leading the development of AstraZeneca’s gout portfolio, including lesinurad and RDEA3170.