FDA批准Tecfidera治疗多发性硬化症

美国食品药品管理局(FDA)已批准一种新的每日2次口服药物——富马酸二甲酯用于治疗复发缓解型多发性硬化症(RRMS)。

将以Tecfidera作为商品名上市的该药物被认为具有预防大脑氧化应激的作用。此外，试验证据表明，它还具有抗炎和神经保护剂的作用。

Tecfidera将成为众多已获批的MS治疗药物之一。根据美国多发性硬化症学会(NMSS)资料，两种剂型的干扰素β-1a(Avonex 和Rebif)以及两种剂型的β-1b(Betaseron和Extavia)已获准用于RRMS治疗，此外获批的药物还包括醋酸格拉替雷(Copaxone)、芬戈莫德(Gilenya)和特立氟胺(Aubagio)。那他珠单抗(Tysabri)也获准用于RRMS治疗，但附带了限制条件。米托蒽醌(Novantrone)获准用于继发进展型、进展复发型和复发缓解型MS治疗。达伐吡啶(Ampyra)被批准用于改善MS患者的行走能力。

FDA药物评价和研究中心神经类产品室主任Russell Katz博士在声明中指出：“由于没有能治愈MS的药物，因此向患者提供多种治疗选择非常重要。”

FDA称，MS是导致年轻成人神经性残疾最常见的原因之一，且女性患病率高于男性。大约400,000美国人罹患该病，而复发缓解型是最常见的。其特点是患者功能日益恶化，随后进入恢复期，但随着时间推移，恢复期越来越不完整，导致功能逐步下降和残疾增加。

富马酸二甲酯的获批是基于纳入2,600多例患者的DEFINE和CONFIRM这2项Ⅲ期临床试验的结果。DEFINE研究结果和CONFIRM研究结果分别在2011年第4届MS合作会议和2012年ECTRIMS/ACTRIMS联合大会上进行了报告。

Biogen Idec公司称，在DEFINE研究中，富马酸二甲酯服用者复发率和残疾率分别减少49%和38%，而CONFIRM研究服药者复发率减少34%。2项研究均表明，与安慰剂相比，富马酸二甲酯可显著减少大脑损伤。

克利夫兰医学中心Mellen多发性硬化症中心医学主任Robert Fox博士在Biogen公司的声明中称：“在临床试验中，与安慰剂组患者相比，富马酸二甲酯治疗患者疾病活动性下降，无论他们是MS早期患者还是更为确切的患者。该药物为医生提供了针对不同MS阶段患者的又一种重要治疗选择。”Fox博士是CONFIRM研究的首席研究员，还是Biogen Idec公司其他项目的有偿顾问。

FDA称，富马酸二甲酯可降低淋巴细胞计数，但没有证据表明服药患者感染增加。建议在开始治疗前以及此后每年监测患者的淋巴细胞计数。面部潮红和胃肠道不适是最常见不良反应。

Biogen Idec公司称，该药物将在数日内投放市场。初始推荐剂量为120 mg，2次/日，口服给药；1周后，推荐剂量增至240 mg，2次/日。

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By: ALICIA AULT, Internal Medicine News Digital Network

The Food and Drug Administration has approved a new, twice-daily oral medication, dimethyl fumarate, for relapsing-remitting multiple sclerosis.

The drug, to be marketed as Tecfidera, is thought to defend the brain against oxidative stress, and experimental evidence has suggested that it may also act both as an anti-inflammatory and as a neuroprotective agent.

Tecfidera joins a host of already approved medications for MS. Two forms of interferon beta-1a (Avonex and Rebif) and two forms of interferon beta-1b (Betaseron and Extavia) have been approved for the relapsing-remitting form, as has glatiramer acetate (Copaxone), fingolimod (Gilenya), and teriflunomide (Aubagio). Natalizumab (Tysabri) is approved for relapsing-remitting MS, but with restrictions. Mitoxantrone (Novantrone) is approved for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS, according to the National MS Society. Dalfampridine (Ampyra) is approved to improve walking in individuals with MS.

"No drug provides a cure for multiple sclerosis, so it is important to have a variety of treatment options available for patients," said Dr. Russell Katz, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

According to the FDA, MS is among the most common causes of neurologic disability in young adults and occurs more frequently in women than men. Some 400,000 Americans are living with the condition, and the relapsing-remitting form is the most common. That is characterized by episodes of worsening function, followed by recovery periods. But recovery periods become less complete over time, leading to progressive decline in function and increased disability.

Dimethyl fumarate was approved based on results from two phase III trials that enrolled more than 2,600 patients: DEFINE and CONFIRM. DEFINE data were originally reported at the Fourth Cooperative Meeting on Multiple Sclerosis in 2011 and the CONFIRM data were reported at the Joint Congress of ECTRIMS/ACTRIMS in 2012.

According to Biogen Idec, which makes dimethyl fumarate, relapses were reduced by 49% in patients taking the drug in the DEFINE trial, and disability by 38%. Relapses declined by 34% in the CONFIRM study. In both trials, dimethyl fumarate significantly reduced lesions in the brain, when compared with placebo.

"In clinical trials, patients treated with dimethyl fumarate had less disease activity when compared to patients on placebo – whether they were in the early stages of MS or had more established disease," said Dr. Robert Fox, medical director of the Mellen Center for Multiple Sclerosis at Cleveland Clinic, in a Biogen statement. Dr. Fox was the lead investigator of the CONFIRM study, and is a paid adviser for Biogen Idec for projects not related to dimethyl fumarate. "This drug provides physicians with an important additional treatment option for their patients across the MS spectrum," Dr. Fox said.

The FDA said that dimethyl fumarate decreases lymphocyte counts, but that there was no evidence of an increase in infections in patients taking the drug in trials. The agency recommends monitoring lymphocyte counts before starting therapy, and annually thereafter. Flushing and gastrointestinal problems were the most common adverse reactions.

Biogen said the drug would be available in a matter of days. The recommended starting dose is 120 mg twice a day orally. After a week, the recommended dose increases to 240 mg twice daily.