此次申请是以药物的两项III期临床实验为基础，实验结果均显示，采用这种缓释制剂治疗的两组受试组患者当中，34.8%和42.9%的人在行走速度方面可以持续得到改善，速度分别加快25.2%和24.7%，而两个安慰剂对照组在这方面得到改善的人数比例仅为8.3%和9.3%，速度仅增加了4.7%和7.7%。

Biogen公司拥有Fampridine-PR在美国以外地区的许可权，该药由Acorda制药公司研发，去年10月份得到了FDA顾问团的批准推荐，今年1月22日它是否能获准将最终揭晓。

Fampridine-SR – Treatment for Multiple Sclerosis

Key Data
Drug (Brand/Generic)Fampridine-SR (4-aminopyridine)Company/LicenseeAcorda TherapeuticsTherapy ClassPotassium channel blockerProduct DescriptionSelective neuronal potassium (K+) channel blockerCurrent IndicationTreatment of MSMarket SectorCNSDevelopment StatusPhase III trials involving MS patients completed; NDA under review by the US FDAFull specifications

Developed by Acorda Therapeutics and manufactured by Elan Corporation, fampridine-SR is a selective neuronal potassium (K+) channel blocker under investigation for the treatment of multiple sclerosis (MS) and spinal cord injury (SCI).

Fampridine-SR, a slow-release formulation of 4-aminopyridine, has a longer half-life and lower peak serum levels than immediate release formulations. It has been developed to increase duration of therapeutic effect and reduce dosing burden, as well as to reduce the incidence and severity of drug-related adverse events.

Phase III clinical trials are ongoing in MS and SCI patients. Positive results were announced from the second Phase III trials of the drug involving MS patients, on walking ability, in June 2008.

Acorda's new drug application (NDA) to the US Food and Drug Administration requesting priority review and a Prescription Drug User Fee Act (PDUFA) dated 22 October 2009 was accepted on 6 May 2009. The NDA was submitted on 30 January 2009.

The company obtained a new active substance status grant for the drug from the European Medicines Agency (EMEA) in June 2009. The agency also granted the company's eligibility to submit a marketing authorisation application (MAA) for fampridine-SR.

In June 2009, Acorda collaborated with Biogen Idec, a developer and manufacturer of therapies, to develop and commercialise fampridine-SR outside the US. Fampridine-SR and other aminopyridine products developed under the agreement will be commercialised by Biogen Idec. The company is also responsible for future clinical developments of fampridine-SR in markets outside the US.

Acorda has received milestone payment of $110m from Biogen and is eligible to receive another $400m. Acorda and Elan's subsidiary Elan Pharma International entered into a supply agreement through which Elan continues to commercially manufacture fampridine-SR. Acorda will pay Elan 7% of the royalty received from Biogen Idec.

In the same month, the new sclerosis drug from Acordawasqualifiedforacentralised regulatory review in Europe.

Demyelinating diseases
MS is an inflammatory autoimmune-mediated disease of the nervous system characterised by recurrent relapses followed by periods of remission. After trauma, it is the second most common neurological disability to affect young and middle-aged adults. It affects twice as many women as men, with the relapsing forms of MS the most common.

"Data from trials showed that treatment with fampridine-SR led to an improvement in walking speed and a significant improvement in leg muscle strength."Patients with MS display a range of symptoms that arise from demyelination (loss of myelin sheath) in the central nervous system (CNS), which includes the brain, spinal cord and optic nerves.

While symptoms vary between patients, they commonly include blurred vision, slurred speech, numbness or tingling in the limbs and problems with balance and coordination, due to the loss of control over vital functions such as seeing, walking and talking.

Prominent inflammatory and autoimmune responses are also evident in patients with traumatic and compressive SCI, in whom there may also be demyelination.

Demyelination alters the structural and functional relationships of voltage-gated ion channels along the axonal membrane of the nerve cell.

Exposed channels cause potassium ions to leak, so causing the axon to 'short circuit'. By closing exposed potassium channels in these damaged nerve fibres, fampridine-SR enables the axon to transmit nerve impulses again.

Clinical trials point to efficacy in MS and SCI
Fampridine-SR advancement to Phase III development in MS was completed in 2009, following encouraging results from earlier Phase II trials. Data from these trials showed that in comparison with placebo, treatment with fampridine-SR led to an improvement in walking speed and a significant improvement in leg muscle strength. Impaired walking and muscle weakness are two of the most common and devastating aspects of MS.

The Phase III programme included the MS-F204 trial, in which fampridine-SR was administered to 240 MS patients. In this trial the safety of fampridine-SR was evaluated together with its effectiveness in improving walking ability. A consistent improvement in walking speed as measured by the timed 25ft walk was the primary outcome measure, with the lower extremity manual muscle test a secondary endpoint.

Improvements over placebo were also observed in the two trials in which fampridine-SR was administered to SCI patients, although the results failed to reach statistical significance for the two primary endpoints: reduction of spasticity as measured by the Ashworth score and improvement of patients' Subject Global Impression (SGI) rating. Despite these results, Acorda Therapeutics remains committed to the continued development of fampridine-SR for SCI.

Expanding treatment options for MS
The advent of the first generation of disease-modifying drugs, which include interferon beta-1a and 1b as well as glatiramer acetate, represented an important advance in the treatment of MS when introduced into clinical practice. Approved for the treatment of relapsing forms of MS, they reduce the frequency and severity of exacerbations as well as the number of lesions seen on magnetic resonance imaging (MRI).

"By closing exposed potassium channels in damaged nerve fibres, fampridine-SR enables the axon to transmit nerve impulses again."However, while these agents have an immunomodulatory effect that alters the course of the disease, they do not reverse the neurological damage that occurs in MS. Currently, no marketed treatments for MS can produce remyelination and so treatment aims to:

•Reduce the rate of relapse
•Prevent fixed disability directly associated to relapse
•Provide symptomatic management of fixed neurological deficits
•Prevent disability arising from disease progression
Results from trials on fampridine-SR suggest that it may have a beneficial effect on walking and muscle weakness, symptoms of the disease that are not well met by available therapies.

Marketing commentary

MS is a chronic and disabling disease, with healthcare costs disproportionate to the numbers affected. In the US alone, costs are estimated to exceed $10bn a year. Walking impairment is a pervasive and seriously debilitating effect of MS. Treatments that have potential to address muscle weakness and improve walking ability could make a significant contribution to improved quality of life in MS and other demyelinating diseases.

氨吡啶缓释剂—多发性硬化症治疗新药
 
美国研究显示，钾通道拮抗剂氨吡啶(fampridine SR)缓释制剂在多发性硬化(MS)患者的一个研究亚组中提示能改善患者行走能力。

在这项随机多中心试验中，206例多发性硬化患者接受氨吡啶缓释制剂10毫克(52例)，15毫克(50例)或20毫克(57例)，或者安慰剂，每日两次，共12周。研究发现，虽然氨吡啶缓释制剂各个剂量组患者平均行走速度都比安慰剂组有较大的改善，但没有一个达到显著性差异。然而，对参与超过3次治疗的患者进行事后分析发现，氨吡啶缓释制剂10毫克、15毫克及20毫克组中步行速度改善的患者比例均显著高于安慰剂组(分别为35.3%、36.0%及38.6%比8.5%)。

美国罗切斯特大学《柳叶刀》报道，口服氨吡啶缓释片治疗多发性硬化症的三期临床试验结果表明，氨吡啶(4-氨基吡啶)能改善多发性硬化征患者的运动功能。

这是一项随机、多中心、双盲对照的三期临床试验。301例多发性硬化症患者随机分为治疗组(氨吡啶10mg，每天两次，疗程14周;229例)和安慰剂组(72例)。结果测治疗前后25英尺步行时间，治疗组改善率(78/224，35%)高于对照组(6/72，8%;p<0.0001)；步速改善率治疗组(25.2%)也优于对照组(4.7%)。试验表明，氨吡啶能有效改善多发性硬化症患者的行走能力，减少患者卧床残疾，具有临床治疗意义。

氨吡啶缓释剂为一口服剂型，每天服2次。它能通过阻滞无髓鞘神经轴突暴露的钾通道而恢复神经传导功能，能以浓度依赖方式增加I型星形细胞、神经元和骨骼肌胞质中游离钙的浓度，并使钙进入星形细胞及肌肉细胞的量增高7倍，但对神经元无此作用。

Fampridine（Fampridine-PR）氨吡啶

药物（品牌/通用）Fampridine -简（4 -氨基）公司/ LicenseeAcorda TherapeuticsTherapy ClassPotassium渠道blockerProduct DescriptionSelective神经元钾（K +）通道blockerCurrent的MSMarket SectorCNSDevelopment StatusPhase三，涉及审判IndicationTreatment MS患者完成;审查新药由美国FDAFull规格

开发阿索尔达治疗和Elan公司fampridine，简制造的是一种选择性的神经元钾（K +）通道的下多发性硬化症（MS）和脊髓损伤（SCI）的治疗调查拦截器。

Fampridine -，一个缓慢释放的4制订简-氨基，具有更长的半衰期比和更低的峰值立即释放血清制剂。它已经开发出来，提高治疗效果的持续时间，减少用药的负担，并降低发病率和严重毒品有关的不良反应。

第三阶段的临床试验正在MS和脊髓损伤患者。宣布了积极的成果从第二第三阶段涉及多发性硬化症患者的药物试验，在行走能力，在2008年6月。

阿索尔达的新药申请（NDA）美国食品和药物管理局要求优先审查和处方药使用者费用法案（PDUFA）日期2009年10月22日被接受，2009年5月6日。提交的新药于2009年1月30号。

该公司2009年6月获得了由欧洲药品局（EMEA）的药物活性物质的新状态的资助。该机构还授予该公司的申请提交上市许可申请（MAA），用于fampridine，简。

2009年6月，阿索尔达与Biogen Idec公司合作，开发和生产的疗法，开发和商业化fampridine，美国以外的简。 Fampridine - SR和根据该协议开发的其他产品将氨基由Biogen Idec公司商业化。该公司还负责为今后的临床发展的fampridine在市场简美国以外。

阿索尔达收到了生物遗传的一个里程碑支付的1.1亿美元，并有资格再次收到4亿美元。阿索尔达和Elan公司的子公司伊兰制药国际签订了供货协议，通过该义隆继续商业生产fampridine，简。阿索尔达将于义隆7 Biogen Idec公司收到的版税％。

在同一个月，从阿索尔达新硬化症的药物是有资格在欧洲的一个中央管理部门的审查。

脱髓鞘疾病
MS是一种炎症性自身免疫性了按缓解期后经常复发的特点介导的神经系统疾病。伤后，这是第二个最常见的神经障碍影响到青年和中年人。它会影响男性的两倍，许多妇女，与微软的复发最常见的形式。

“从试验的数据表明，fampridine治疗简导致了步行速度和腿部肌肉的力量在显着改善的改善。”多发性硬化症患者的症状表现出一系列的脱髓鞘出现（亏损髓鞘中枢神经）系统（CNS），其中包括脑，脊髓和视神经。

虽然症状的患者之间各有不同，但通常包括视力模糊，含糊，如看到讲话，麻木或四肢和平衡和协调问题，刺痛，由于控制重要功能丧失，走路和说话。

突出炎症和自身免疫性反应，也表现在脊髓外伤性和压缩，病人在其中可能也有脱髓鞘。

脱髓鞘改变电压的结构和功能的关系，沿神经细胞轴突膜离子通道。

暴露钾离子通道导致泄漏，因此导致轴突的'短路'。关闭暴露了这些受损的神经纤维，fampridine，简使轴突传递神经冲动再次钾通道。

临床试验点，在MS和脊髓损伤的疗效
Fampridine -简晋级第三阶段的发展，在MS在2009年完成后，从早期阶段第二期临床试验结果令人鼓舞。从这些试验的数据表明，与安慰剂比较，以fampridine治疗简导致了步行速度和腿部肌肉的力量在显着改善的改善。受损步行和肌肉无力的MS是最常见的和毁灭性的两个方面。

第三阶段方案，包括在MS - F204的审判，其中fampridine，简是管理240多发性硬化症患者。在这方面的fampridine安全简进行了评估其在提高效益一起行走能力的审判。阿在步行由定时二十五英尺步行速度测量的是持续改善的主要成果的措施，以下肢肌肉测试手册次要终点。

改进对安慰剂也观察到的两种fampridine，简是管理的脊髓损伤病人的审判，但结果未能达到两个主要终点统计意义：痉挛减少由阿什沃思评分和病人的科目的改善来衡量总体印象（SGI）的评级。尽管取得了这些成绩，阿索尔达治疗仍然致力于继续发展的fampridine为脊髓损伤简。

扩大治疗多发性硬化症的选择
在疾病的第一代的出现改变的药物，其中包括干扰素β- 1a和1b以及醋酸格拉默，代表了在治疗多发性硬化症的重要进展，当引入到临床实践。对多发性硬化症复发的批准用于治疗，减少他们的病情加重的频率和严重程度以及对磁共振成像可见病灶数目（核磁共振）。

“通过关闭暴露了受损神经纤维，fampridine钾通道，简使轴突传递神经冲动了。”然而，尽管这些药物具有免疫调节作用，可以改变这种疾病的过程中，他们并没有扭转发生神经损伤在MS。目前，市场上没有为MS治疗可产生髓鞘，所以治疗的目的是：

•降低复发率
•固定残疾预防复发直接相关
•提供固定的神经功能缺损症状的管理
•预防残疾恶化引起的疾病
从fampridine试验结果，简表明，它可能对肌肉无力行走和有益的影响，症状认为是没有很好地满足患者提供治疗。

市场评论

多发性硬化症是一种慢性致残性疾病的医疗费用不相称，受影响。仅在美国，费用估计将超过100亿美元一年。散步减损的MS普遍和严重的破坏性影响。治疗有潜力的肌肉无力解决和改善行走能力可以作出重大贡献的MS和其他脱髓鞘疾病，提高生活质量。