FDA批准第二个口服过敏治疗药物Grastek

美国食品药品管理局（FDA）已批准舌下免疫治疗药物Grastek，用于草花粉引起的伴有或不伴有结膜炎的5~65岁过敏性鼻炎患者。

默克公司生产的Grastek（梯牧草花粉过敏原提取物）于去年12月获得FDA专家委员会一致支持，这也是FDA最近几周批准的第二个舌下口服治疗药物。4月1日，FDA 批准了格里尔实验室（Greer Laboratories）的Oralair，该药物含有5种草花粉的冷冻干燥提取物：肯塔基蓝草、鸭茅、多年生黑麦草、甜春季草和梯牧草，获准用于10~65岁患者。

如同Oralair，Grastek也附带了一项可能导致严重过敏反应的黑框警告。Grastek还禁用于严重、不稳定性或未得到控制的哮喘患者，任何严重全身性过敏反应史患者，对舌下过敏原免疫治疗药物有任何严重局部反应史患者或对该药物非活性成分过敏者。

梯牧草（Phleumpratense）是一种常见的、分布广泛的长茎草，耐寒性强。据默克公司称，梯牧草与其他草类交叉反应，包括甜春季草、鸭茅、多年生黑麦草、肯塔基蓝草、牛尾草以及小糠草。

默克公司称，患者在接受治疗前，应通过皮肤试验或体外试验确认梯牧草或其他交叉反应草花粉特异性IgE抗体阳性。在草花粉季节来临前12周开始服药治疗，每日舌下1片，并持续整个季节。患者首次服药应在医生监督下进行，后续可在家中自行服用，但应给患者开具肾上腺素注射剂，并给予患者自助注射器使用方面的培训。

默克公司称，可在连续3年内每日服用Grastek。

在临床试验中，无论是成人还是儿童患者，最常见不良反应包括口部瘙痒、咽喉刺激和口腔水肿。成人患者还可出现耳部瘙痒。

FDA批准的药物效价为2800个梯牧草花粉提取物生物当量过敏原单位（BAU），规格为10片泡罩包装。FDA还在批准信中要求默克公司向患者提供用药指南，因为该产品“存在严重且重大的公共健康方面的担忧。”

另外，FDA还要求默克公司开展一项为期3年、纳入10,000例患者的上市后研究，以评估该药物的安全性，并于2017年左右完成。同时要求默克公司2017年前完成另外一项上市后研究，考察通过电子病历确认的10,000例新用药者的安全性。

默克公司称，Grastek将于4月底在美国药店销售。

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The Food and Drug Administration has approved Grastek, a sublingual immunotherapy for grass pollen–induced allergic rhinitis with or without conjunctivitis in individuals aged 5-65 years.

Grastek (Timothy Grass Pollen Allergen Extract), manufactured by Merck, was unanimously supported by an FDA advisory committee in December and is the second sublingual oral therapy to be approved by the agency in a few weeks. On April 1, the FDA approved Greer Laboratories’ Oralair, which contains a mixture of freeze-dried extracts from the pollens of five grasses: Kentucky blue grass, orchard, perennial rye, sweet vernal, and Timothy. That product is approved for individuals aged 10-65 years.

Like Oralair, Grastek has a black box warning of the potential for severe allergic reactions such as anaphylaxis. Grastek is also contraindicated in patients with severe, unstable, or uncontrolled asthma; a history of any severe systemic allergic reaction; a history of any severe local reaction after taking any sublingual allergen immunotherapy; a history of eosinophilic esophagitis; or hypersensitivity to any of the inactive ingredients contained in the product.

Timothy grass (Phleumpratense) is a common, widespread, long-stemmed grass that is very hardy. According to Merck, it is cross reactive with other grasses, including sweet vernal, orchard (also known as cocksfoot), perennial rye, Kentucky blue (also known as June grass), meadow fescue, and redtop.

Before initiating treatment, a patient’s allergy must be confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for Timothy grass or cross-reactive grass pollens. Therapy – at a dose of one tablet sublingually daily – is begun 12 weeks before the grass pollen season and should continue through the season. The first dose should be given under a physician’s supervision, according to Merck. Subsequent doses can be taken at home, but patients should also be prescribed injectable epinephrine and given training in how to use the autoinjector.

The company said that Grastek can be taken daily for up to 3 consecutive years.

In trials, the most common adverse reactions for both adult and pediatric patients included oral pruritus, throat irritation, and mouth edema. Adults also experienced ear pruritus.

The FDA approved production of tablets that have a potency of 2,800 Bioequivalent Allergy Units (BAU) of Timothy Grass pollen extract, which will be supplied in 10-tablet blister packs. The agency also said in its approval letter that it will require Merck to create a Medication Guide for distribution to patients because the product "poses a serious and significant public health concern."

Merck also will be required to conduct a 3-year, 10,000-patient postmarketing study to gauge safety, to be completed by about 2017. A second postmarketing study is also required, looking at 10,000 new users who are identified through electronic medical records. That study is also due to be finished by 2017.

Grastek will be available in U.S. pharmacies in late April, according to Merck.