Actelion肺动脉高压药物Opsumit获欧盟批准

Actelion公司12月20日宣布，药物Opsumit（macitentan，10mg）已获欧盟委员会（EC）批准，作为单药疗法或联合其他药物，用于肺动脉高压（PAH）成人患者（WHO功能分级II-III）的长期治疗。

Opsumit的获批，部分基于具有里程碑意义的III期 SERAPHIN研究的疗效和安全性数据。该项研究表明，与安慰剂相比，Opsumit（macitentan，10mg）治疗组发病率/死亡率事件风险降低45%（p＜0.0001），达到了研究的主要终点。所观察到的疗效，与患者是否已接受其他PAH疗法无关。此外，与安慰剂相比，Opsumit治疗组PAH相关住院或死亡风险降低50%（p＜0.0001）。

SERAPHIN研究中，Opsumit治疗组所观察到的最常见不良反应为：贫血、鼻咽炎/咽炎、支气管炎、头痛、感冒、尿路感染。

此前，Opsumit已分别于今年10月和11月获FDA和加拿大卫生部批准，作为每日一次的疗法，用于治疗肺动脉高压（PAH），以延缓疾病进展。

Opsumit属于一类名为内皮素受体拮抗剂的药物，能够放松肺动脉并降低血压，Opsumit与该类药物中的其他药物一样，具有一个黑框警示，指出该药不可用于孕妇，因为Opsumit可能对胎儿造成伤害。

Opsumit是Actelion公司PAH药物Tracleer的继任者，Tracleer将于2015年失去专利保护。根据Actelion提供的数据，Tracleer在2012年的销售达15亿瑞士法郎，为该公司最畅销的药物。Actelion正指望Opsumit来弥补Tracleer专利到期所致的销售预期下降。

Opsumit将与市面上的其他PAH药物展开竞争，包括吉利德（Gilead）的Letairis，该药在美国以外国家和地区由葛兰素史克（GSK）以品牌名Volibris销售。

肺动脉高压（PAH）是一种极度严重的疾病，症状包括：呼吸短促、易于疲劳、晕厥、胸痛以及腿部和踝部水肿。此外，患者的肺动脉高压会逐步加重，甚至使寿命缩短。多数肺动脉高压相关的症状源自右心衰竭。

英文原文：Actelion’s PAH drug Opsumit approved in EU

—Approval granted by European Commission on 20 December 2013
—Opsumit approved as monotherapy or in combination with another PAH therapy for the long-term treatment of WHO Functional Class II to III PAH patients
—First EU launch planned in Germany in February 2014

ALLSCHWIL, SWITZERLAND - 20 December 2013 - Actelion Ltd (ATLN.VX) today announced that Opsumit® (macitentan), a novel dual endothelin receptor antagonist (ERA), has been granted marketing authorisation for the long-term treatment of PAH in the EU by the European Commission. Opsumit, as monotherapy or in combination, is indicated for the longterm treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III. 

Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.

Macitentan 10mg is also described as reducing the risk of PAH related death or hospitalization for PAH up to end of treatment (EOT) by 50% (HR 0.50; 97.5% CI: 0.34 to 0.75; logrank p

Dr Nazzareno Galiè from the Institute of Cardiology, University of Bologna, Bologna, Italy spoke of the impact of the availability of Opsumit, "We are all very pleased with the approval of Opsumit in Europe. For the first time we can offer patients a therapy that has demonstrated improvement in long term clinical outcome showing a significant effect in naive patients and patients who are already on a specific PAH treatment."

The EU label was based in part on data from the landmark Phase III SERAPHIN study which was published in the New England Journal of Medicine in August 2013, the SERAPHIN study demonstrated that treatment with macitentan 10 mg resulted in a 45% risk reduction (hazard ratio [HR] 0.55; 97.5% CI: 0.39 to 0.76; p

Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "We are delighted with today`s announcement as we believe that Opsumit represents a major step forward for the management of PAH. Our company strategy of sustaining and growing our PAH franchise has yet again been bolstered by this approval. This achievement marks a significant moment for the PAH community in Europe as the first and only PAH treatment with proven long-term efficacy, from controlled clinical trials in PAH, and will now offer hope of a better future to those living with this disease. Actelion is now working to make this important medicine available to patients around European markets in the coming months."

The most commonly reported adverse drug reactions are nasopharyngitis (14.0%), headache (13.6%) and anaemia (13.2%). The majority of adverse reactions are mild to moderate in intensity.

Opsumit was approved by the FDA on 18 October 2013 and by Health Canada in November 2013. It is also undergoing regulatory assessment in other countries including Switzerland. )