PTC制药8月4日宣布，药物Translarna（ataluren）获欧盟委员会（EC）有条件批准（conditional approval），用于5岁及以上无义突变型杜氏肌营养不良（nmDMD）非卧床（ambulatory，能走动的）患者的治疗。此次批准，适用于欧盟28个成员国以及欧洲经济区成员国，包括冰岛列支敦士登和挪威。作为有条件上市的一部分，PTC有义务完成在nmDMD中开展的验证性III期ACT DMD研究，并提交来自该研究的额外疗效和安全性数据。
今年1月，欧洲药品管理局（EMA）人用医药产品委员会（CHMP）曾给予Translarna消极意见，随后PTC公司提交额外分析数据，要求重新审查，之后CHMP于今年5月建议有条件批准Translarna。此前，FDA已授予Translarna孤儿药地位。
Translarna的获批，是基于一项IIb期研究的数据及后续分析数据。该项研究是一项48周、安慰剂对照、双盲试验，在174例无义突变型杜氏肌营养不良（nmDMD）患者中开展。数据表明，与安慰剂治疗组相比，Translarna（40mg/kg/天）治疗组6分钟步行距离（6MWD）平均增加31.3米，下床活动下滑速率也较慢。安全性数据表明，Translarna一般耐受性良好，严重不良事件少见。
目前，PTC公司正在开展III期ACT DMD临床研究。
Translarna是一种蛋白质修复药物，开发用于由无义突变所致遗传性疾病的患者群体，旨在使含有无义突变的基因，产生功能性蛋白。若基因中存在无义突变，会导致蛋白质合成提前终止，产生无功能的蛋白。目前，Translarna正开发用于囊性纤维化（CF）和杜氏肌营养不良（DMD）的治疗。
英文原文：
PTC Therapeutics Receives Conditional Approval in the European Union for Translarna™ For the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy
SOUTH PLAINFIELD, NJ – August 4, 2014 – PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that the European Commission has granted conditional marketing authorization for Translarna™ (ataluren), in the European Union (EU) for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged five years and older.
"We are delighted that Translarna was approved for the treatment of nonsense mutation Duchenne muscular dystrophy. By targeting the underlying cause of DMD, it has the potential to change the course of the disease. We are moving rapidly to make this product available to patients in the EU as we continue our global efforts to fulfill our vision of making Translarna available to all the boys it may benefit," stated Stuart W. Peltz, Ph.D., CEO of PTC Therapeutics, Inc. "We are grateful to the patients, families, advocacy groups and physicians who have supported PTC Therapeutics through many years of research and development of Translarna. The DMD community has been waiting a long time for treatment options and this conditional approval marks an important day for us all."
The authorization allows PTC to market Translarna in the 28 countries that are Member States of the European Union, as well as European Economic Area members Iceland, Liechtenstein and Norway. As part of the conditional marketing authorization, PTC is obligated to complete its confirmatory Phase 3 trial in nmDMD (ACT DMD) and submit additional efficacy and safety data from the trial.
The approval is based on the safety and efficacy results from a randomized double-blind multicenter study in 174 nmDMD patients for 48 weeks and our additional retrospective analyses of study data. The primary endpoint evaluated the effect of Translarna on ambulation as assessed by the change in distance walked (six-minute walk distance - 6MWD) during a six-minute walk test (6MWT). The post-hoc analysis showed that from baseline to Week 48, patients receiving Translarna (40 mg/kg/day given in 3 doses) had a 12.9 meter mean decline in 6MWD, and patients receiving placebo had a 44.1 meter mean decline in 6MWD. Thus the mean change in observed 6MWD from baseline to Week 48 was 31.3 meters better in the Translarna group than in the placebo group (p=0.056). Furthermore, in more severely affected patients whose baseline 6MWD was less than 350 meters, the mean change in observed 6MWD from baseline to Week 48 was 68 meters better in the Translarna group than in the placebo group. Patients on Translarna also showed a slower rate of decline in ambulation based on an analysis of time to 10 percent worsening in 6MWD. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency found that these results suggest that Translarna slows the loss of walking ability in nmDMD patients.
Additionally, based on a retrospective analysis, patients receiving treatment also trended better in secondary endpoints such as stair climb and stair descend time-function tests, which the CHMP also found to suggest slowing of nmDMD progression relative to placebo. Safety results showed that Translarna was generally well tolerated. Serious adverse events were infrequent, and none was considered to be related to Translarna. The most frequent adverse reactions at the recommended dose were nausea, vomiting, and headache. These adverse reactions generally did not require medical intervention, and no patients discontinued Translarna treatment due to any adverse reaction.
"The world's first approved treatment for the underlying cause of DMD marks a very important moment for patients and their families. It is our highest priority to make Translarna available to patients and we will be working with regulators, payers, physicians and patient organizations to make that a reality." stated Mark Rothera, Chief Commercial Officer, of PTC Therapeutics, Inc.
ABOUT DUCHENNE MUSCULAR DYSTROPHY (DMD)
Primarily affecting males, Duchenne muscular dystrophy (DMD) is a progressive muscle disorder caused by the lack of functional dystrophin protein. Dystrophin is critical to the structural stability of skeletal, diaphragm, and heart muscles. Patients with DMD, the more severe form of the disorder, lose the ability to walk as early as age 10 and experience life-threatening lung and heart complications in their late teens and twenties. It is estimated that a nonsense mutation is the cause of DMD in approximately 13% of patients, or approximately 2,000 patients in the United States and 2,500 patients in the European Union. More information about DMD is available through the Muscular Dystrophy Association (www.mdausa.org), Parent Project Muscular Dystrophy (www.parentprojectmd.org), Action Duchenne (www.actionduchenne.org), United Parent Projects Muscular Dystrophy (uppmd.org), Muscular Dystrophy Campaign (www.muscular-dystrophy.org) and AFM (l'Association française contre les myopathies), (www.afm-telethon.fr).
ABOUT PTC THERAPEUTICS, INC.
PTC is a biopharmaceutical company focused on the discovery and development of orally administered, proprietary small molecule drugs that target post-transcriptional control processes. Post-transcriptional control processes regulate the rate and timing of protein production and are essential to proper cellular function. PTC's internally discovered pipeline addresses multiple therapeutic areas, including rare disorders, oncology and infectious diseases. PTC has developed proprietary technologies that it applies in its drug discovery activities and in collaborations with leading biopharmaceutical companies. For more information on the company, please visit our website www.ptcbio.com.
