FDA批准屈昔多巴用于治疗神经原性直立性低血压

【FDA批准屈昔多巴用于治疗神经原性直立性低血压】2月18日，FDA批准Chelsea Therapeutics的Northera（屈昔多巴），用于治疗神经原性直立性低血压。临床试验证明该药能够缓解头晕症状，FDA经孤儿药通道、加速批准通道批准该药，药品标签中有黑框警告提醒该药导致的高血压风险。

商品名：Northera  通用名：droxidopa  中文名：屈昔多巴

审批分类：孤儿药+加速批准

药企：Chelsea Therapeutics Inc

适应症：原发性自主神经功能衰竭（帕金森病、多系统萎缩、单纯性自主神经衰竭）、多巴胺β羟化酶缺乏症、非糖尿病自主神经病变引起的神经原性直立性低血压（neurogenic orthostatic hypotension），症状为直立性眩晕。

剂型规格：本品为片剂，有100 mg、200 mg、300 mg三个规格，推荐剂量为300 mg/天，分三次口服。

活性成分：屈昔多巴，结构式如下：

                               
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作用机理：屈昔多巴是一种合成的氨基酸，在体内被多巴胺脱羧酶代谢成去甲肾上腺素，去甲肾上腺素能够升高血压。

临床试验：一项关键临床试验入组了171例患者，随机分成屈昔多巴组、安慰剂组，其中147例患者的数据用于有效性分析。以OHSA Item 1评分为指标，屈昔多巴组、安慰剂组患者初始评分均为5.1，经过1周治疗后，屈昔多巴组比安慰组多降低0.9个评分（P=0.028）。

黑框警告：卧位高血压。

不良反应：卧位高血压、高烧、缺血性心脏病、心律失常、充血性心力衰竭、过敏反应、头痛、头晕、恶心、疲乏。

相关专利：待补。

补充说明：屈昔多巴最初由Sumitomo Pharmaceuticals（现属Dainippon Sumitomo）研发，1989年后在日本及亚洲其他地区获批，用于治疗神经原性直立性低血压、透析相关低血压，2006年Dainippon Sumitomo将日本、中国、韩国、台湾以外的权利许可给Chelsea Therapeutics。国内重庆圣华曦药业于2012年首仿（3+3）上市，商品名善为，目前尚无其他厂家申报。

FDA批准首个神经源性体位性低血压药物Northera
关键词： Chelsea制药 Northera droxidopa 神经源性体位性低血压



2014年2月20日讯 /生物谷BIOON/ --Chelsea制药2月18日宣布，FDA已授予药物Northera（droxidopa，屈昔多巴）加速批准，用于原发性自主神经衰弱（帕金森病，多系统萎缩症和纯自主神经衰弱）、多巴胺β羟化酶缺乏症、非糖尿病性自主神经病变等患者有症状神经源性体位性低血压（NOH）的治疗。

Northera是首个也是唯一一个获FDA批准用于NOH治疗的药物，也是近20年NOH对症治疗的首个新治疗选择。此前，FDA已授予Northera孤儿药地位，并进入FDA特殊快速通道。特殊快速通道旨在加快那些用于治疗严重或潜在危险生命的疾病的尚未满足医疗需要的药物的审评。

Northera（Droxidopa）是Chelsea制药的主打研究药物，开发用于治疗原发性自主神经衰弱（如帕金森病、多系统萎缩和单纯性自主神经衰弱）患者的有症状神经源性直立性低血压症状（NOH）。Droxidopa是一合成儿茶酚胺，通过脱羧直接转化为去甲肾上腺素，使得中枢和外周神经系统去甲肾上腺素水平升高。

关于有症状神经源性直立性低血压（NOH）：

据估计，在美国和欧盟，有近30万患者患有慢性有症状NOH。有症状NOH是一种慢性疾病，由内在性神经性疾病导致，如帕金森氏病、多系统萎缩症或纯自主神经衰弱。NOH的症状包括头晕、胸闷、视力模糊、乏力、注意力不集中以及站立时昏厥发作。这些症状往往严重限制一个人开展日常活动的能力，患者不得不依靠轮椅生活。（生物谷Bioon.com）

英文原文：Chelsea Therapeutics Announces FDA Accelerated Approval of NORTHERA™ (Droxidopa) for the Treatment of Symptomatic NOH

—First New Treatment Option for Symptomatic NOH in Nearly Two Decades

—First and Only FDA Approved Therapy to Demonstrate Symptomatic Benefit in Patients with NOH

CHARLOTTE, N.C.--(BUSINESS WIRE)--Chelsea Therapeutics International, Ltd. (Nasdaq: CHTP) today announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval of NORTHERATM (droxidopa) for the treatment of symptomatic neurogenic orthostatic hypotension (NOH). NORTHERA is the first and only therapy approved by the FDA which demonstrates symptomatic benefit in patients with NOH.

NORTHERA is indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic NOH caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy and pure autonomic failure), dopamine beta hydroxylase deficiency and non-diabetic autonomic neuropathy.

“The approval of NORTHERA is an extraordinary achievement, one for which I thank patients and their families, investigators and the medical community, our partner Dainippon Sumitomo, and our employees,” said Joseph G. Oliveto, President and Chief Executive Officer of Chelsea Therapeutics. “We will now turn our efforts towards delivering NORTHERA to patients with NOH in the United States, an important goal we expect to achieve in the second half of the year.”

Symptomatic NOH is an autonomic nervous system disorder caused by failure to produce and or release adequate amounts of norepinephrine upon standing. Norepinephrine deficiency results in an inability for a person to maintain adequate blood pressure and blood flow to the brain when upright, frequently resulting in dizziness, lightheadedness, blurred vision, fatigue, poor concentration and fainting episodes. These symptoms often severely limit a person's ability to perform routine daily activities that require standing or walking for both short or long periods of time. 1,2 The disorder affects an estimated 80,000 to 150,000 individuals in the United States.

“Symptomatic NOH is a commonly debilitating disorder with limited treatment options and no new therapeutic choices introduced in nearly two decades," commented Dr. Robert A. Hauser, Professor of Neurology, Molecular Pharmacology, and Physiology, and Director of the Parkinson's Disease Movement Disorders Center, University of South Florida. “NORTHERA has a distinct mechanism of action affecting the root cause of NOH and represents an important new treatment choice for patients. It is the first and only therapy approved to address specific underlying symptoms of NOH, namely orthostatic dizziness, lightheadedness, or feeling like you might black out. I look forward to offering this new and novel treatment approach to patients who may benefit from it.”

“This approval is a significant step forward for people with MSA forced to cope with the debilitating effects of NOH,” said Judy Biedenharn, Co-President of the Multiple Systems Atrophy (MSA) Coalition. “Addressing the major symptoms of NOH can have an impact on a person’s ability to perform even the simplest of daily activities -- like taking a shower or standing to brush one’s teeth -- offering an important benefit to both individuals and their caregivers.”

The NORTHERA approval was granted under the FDA’s accelerated approval program, which allows for conditional approval of a medicine that fills a serious unmet medical need, provided additional confirmatory studies are conducted. The package insert indicates that effectiveness beyond 2 weeks of treatment has not yet been demonstrated, therefore the continued effectiveness of NORTHERA in patients should be assessed periodically. A multi-center, placebo-controlled, randomized study, which includes a 4 week randomized withdrawal phase preceded by a three month open label run-in phase, designed with the goal of definitively establishing the durability of the clinical benefits of NORTHERA, has been preliminarily agreed to with the FDA. Based on the contemplated study design, the trial would include approximately 1,400 patients, which the FDA has agreed may be enrolled over a six year period.

(责任编辑：lishuheng)