老药新用：Santhera提交艾地苯醌用于杜氏肌营养不良申请

1.2019年5月27日，Santhera Pharmaceuticals (SIX: SANN)宣布提交Puldysa® (idebenone)（艾地苯醌）有条件上市申请，适应症为杜氏肌营养不良症（Duchenne muscular dystrophy，DMD）相关的呼吸功能障碍。 Idebenone)（艾地苯醌）在欧洲和美国获得孤儿药资格认定；另外在美国也获得快速通道上市资格。老药新用，同样有很大威力。

2.杜氏肌营养不良症（Duchenne muscular dystrophy，DMD），是X染色体上Xp21处基因突变导致的非常常见并且非常严重的肌营养不良症。DMD主要是男性患病，据统计全球大约每3,600个男孩中就有一人患有这种疾病。DMD是一种与生俱来的罕见病。

基因突变导致患者肌肉中缺少抗肌萎缩蛋白（Dystrophin），出现进行性肌肉退化和萎缩，并伴随炎症反应.最终导致心肌病和呼吸衰竭而死亡。

3.目前，用于治疗杜氏肌营养不良症药物有：Sarepta Therapeutics的反义RNA药物Exondys 51（Eteplirsen）、PTC Therapeutics的Translarna（Ataluren），以及泼尼松、泼尼松龙、Deflazacort（地夫可特）等激素类药物。效果有限，治疗费用高昂，该疾病亟需制药企业和公众关注。

2018年5月，我国国家卫生健康委员会等五个部门联合制定的《第一批罕见病目录》公布的121种罕见病中包含了进行性肌营养不良，DMD是该类疾病的常见型别。

4.艾地苯醌最先由日本武田制药（Takeda）开发，一款在1988年获批上市的老药。目前在国内的仿制药主要用于慢性脑血管病及脑外伤等所引起的脑功能损害。

艾地苯醌是一个辅酶Q10的合成类似物，可激活脑线粒体呼吸活性，改善脑缺血的脑能量代谢，改善脑内葡萄糖利用率，使脑内ATP产生增加，抑制脑线粒体生成过氧化脂质，抑制脑线粒体膜脂质过氧化作用所致的膜障碍。

此前欧盟批准了Santhera 的首款药物 Raxone（也是艾地苯醌），用于 Leber 遗传性视神经病变（LHON）青少年及成年患者的视觉障碍治疗。

5.附Santhera原文：

Pratteln, Switzerland, May 27, 2019 – Santhera Pharmaceuticals (SIX: SANN) announces that it has submitted a marketing authorization application (MAA) for Puldysa® (idebenone) for the treatment of respiratory dysfunction in patients with Duchenne muscular dystrophy (DMD) to the European Medicines Agency (EMA). Santhera is seeking conditional marketing authorization (CMA). The indication for Puldysa sought under CMA is the treatment of respiratory dysfunction in patients with DMD who are not using glucocorticoids.

The MAA is supported by data from Santhera’s Phase II (DELPHI) study, the long-term DELPHI-Extension study, the pivotal Phase III (DELOS) study [1-5] and the recently completed SYROS study, a collection of long-term data from patients who completed the DELOS study and continued to be treated with idebenone for up to six years [6]. “The new data included in this regulatory submission confirm clinically relevant patient benefits and long-term therapeutic efficacy with idebenone in patients with DMD. Thereby, we have closed earlier data gaps and respond to requirements from the regulatory authorities,” said Kristina Sjöblom Nygren, MD, Chief Medical Officer and Head of Development at Santhera.

In line with previous communications, Santhera plans to submit a new drug application (NDA) with the US FDA following the completion of the currently ongoing double-blind, placebo-controlled Phase III (SIDEROS) study that investigates the efficacy and safety of idebenone in delaying the loss of respiratory function in patients with DMD taking glucocorticoid steroids over a period of 18 months (ClinicalTrials.gov Identifier: NCT02814019; www.siderosdmd.com). With 266 patients to be enrolled, SIDEROS isthe largest actively recruiting clinical trial in DMD. To date, the study has 214 patients enrolled at approximately 60 clinical trial sites in Europe, the US and Israel, with patient recruitment expected to complete in 4Q 2019. Eligible patients who complete SIDEROS are offered to enroll in the open-label SIDEROS-Extension study (ClinicalTrials.gov Identifier: NCT03603288). Idebenone for the treatment of DMD has been granted orphan drug designation by European, US, Swiss and Australian authorities, and it has fast track designation in the US.

6.更多前沿医药信息，参考：

NMPA/CDE/FDA/EMA；

药融数据，Pharnex Datamonitor；