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新型口服血管舒张药获准用于肺动脉高压

Novel oral vasodilator approved to treat pulmonary hypertension
来源:爱思唯尔 2013-10-14 13:57点击次数:753发表评论

美国食品药品管理局(FDA) 声明指出,拜耳公司的riociguat已于10月8日获准用于治疗成人慢性血栓栓塞性肺动脉高压(CTEPH)和肺动脉高压(PAH),并将以商品名Adempas上市销售。


FDA药物评价与研究中心的Norman Stockbridge博士在声明中称,riociguat是首个获准治疗肺动脉高压的新型可溶性鸟苷酸环化酶(sGC)激动剂,为口服片剂,这也是首个被证明对CTEPH患者有效的药物。


Riociguat属于妊娠用药分级的X级药物,只有通过风险评估与减缓策略(REMS)程序才可用于女性患者。


该药物获批的适应证包括:术后持续性/复发性CTEPH(WHO分级4)或不能手术的CTEPH以改善运动能力和WHO功能分级,以及PAH(WHO分级1)以改善运动能力、改善WHO功能分级和延缓临床恶化。


该批准令是基于2项国际临床研究结果。研究显示,与安慰剂相比,riociguat可显著改善患者6分钟步行测试结果。其副作用包括头疼、头晕、消化不良、外周水肿、恶心、腹泻和呕吐。基于上述结果,FDA专家委员会于今年8月一致推荐批准该药物用于上述2种适应证。


在纳入380例PAH患者的试验中,治疗组12周6分钟步行测试距离与基线相比平均提高30 m,而安慰剂组平均减少6 m。治疗组和安慰剂组WHO功能分级改善比例分别为21%和14%,恶化比例分别为4%和14%。


在纳入261例CTEPH患者的研究中,治疗组16周6分钟步行测试距离与基线相比平均提高39 m,而安慰剂组平均减少6 m。治疗组和安慰剂组WHO功能分级改善比例分别为33%和15%,恶化比例分别为5%和7%。


上述2项研究结果已于7月25发表在《新英格兰医学杂志》上(2013;369:330-40; 2013;369:319-29)。


Riociguat说明书中包括了有关胚胎-胎儿毒性的黑框警告以及女性患者只有通过REMS程序才可获得该药物治疗的内容。


鉴于该药物具有低血压风险,因此禁止与硝酸盐类或一氧化氮供体(如硝酸戊酯)以及磷酸二酯酶抑制剂(PDE)或非特异性PDE同时应用。


拜耳公司发言人称,该药物30天疗程的批发价为7,500美元,1片/次,3次/日。该公司已设立患者援助项目,以帮助用药费用纳入医疗保险体系。


该公司发言人还指出,截至目前,riociguat已在加拿大获准用于WHO功能分级Ⅱ或Ⅲ级的不能手术或术后持续性/复发性CTEPH成人患者,欧盟正在对其上市申请进行审评。


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By: ELIZABETH MECHCATIE, Cardiology News Digital Network


Riociguat, a potent vasodilator that is the first in a new class of drugs, has been approved by the Food and Drug Administration for treating two types of pulmonary hypertension in adults.


The drug, which will be marketed as Adempas, was approved Oct. 8 to treat chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), the agency said in a statement.


Orally administered in tablet form, riociguat is a soluble guanylate cyclase (sGC) stimulator, the first drug in this class to be approved for pulmonary hypertension. It is also "the first drug of any class to be shown to be effective for patients with CTEPH," Dr. Norman Stockbridge, director of the Division of Cardiovascular and Renal Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.


Riociguat is a pregnancy category X drug and is available to women only through a Risk Evaluation and Mitigation Strategy (REMS) program.


The approved indications for the drug, which will be marketed by Bayer HealthCare Pharmaceuticals, are for persistent/recurrent CTEPH (WHO group 4) "after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class" or PAH (WHO group 1) "to improve exercise capacity, improve WHO functional class, and to delay clinical worsening."


Approval was based on the results of two international studies that found treatment resulted in significant improvements over placebo in the 6 minute walk test. Side effects of treatment include headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea, and vomiting, according to the FDA. Based on these results, an FDA advisory panel unanimously recommended approval of the two indications in August.


In the study of 380 patients with PAH, the change from baseline in the 6-minute walk test at 12 weeks improved by a mean of 30 m among those treated with riociguat, vs. a mean drop of 6 m in the placebo group. The WHO functional class improved in 21% of those on riociguat, compared with 14% in the placebo group, deteriorating in 4% and 14%, respectively.


In the study of 261 patients with CTEPH, the change from baseline in the 6-minute walk test at 16 weeks improved by a mean of 39 m among treated patients vs. a mean 6 m reduction in the placebo group at 16 weeks. WHO functional class improved in 33% of those on riociguat and 15% of those on placebo, deteriorating in 5% and 7%, respectively.


The two studies were published in the July 25 issue of the New England Journal of Medicine (2013;369:330-40; 2013;369:319-29).


The prescribing information includes a boxed warning about embryo-fetal toxicity. Women can receive the drug only through the REMS program.


Because of the risk of hypotension, the drug is contraindicated for use with nitrates or nitric oxide donors, such as amyl nitrate, and with phosphodiesterase inhibitors or nonspecific PDE inhibitors.


The wholesale cost of the drug is $7,500 for 30 days of treatment, with one tablet taken three times a day, according to a Bayer spokesperson. The company has set up a patient assistance program to help with coverage.


To date, riociguat has been approved in Canada for the treatment of inoperable or persistent/recurrent CTEPH after surgery in adults with WHO functional class II or III pulmonary hypertension, and it is under review in the European Union, according to the company spokesperson.


Novel oral vasodilator approved to treat pulmonary hypertension


学科代码:心血管病学 呼吸病学 药学   关键词:riociguat 可溶性鸟苷酸环化酶激动剂 肺动脉高压
来源: 爱思唯尔
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