2014-10-22国际临床信息（杂烩）

                          武田/Orexigen在美国推出减肥新药Contrave

                               
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发布日期：2014-10-22  来源：新药汇  

) G# i% T: Z( {7 L' J1 ?$ T3 J) p Orexigen历经3年磨难终获FDA批准，但如何在市场立足，仍面临严峻挑战。
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武田（Takeda）与合作伙伴Orexigen公司近日联合宣布，在美国推出减肥新药Contrave（盐酸纳曲酮与盐酸安非他酮缓释片），该药是FDA于今年9月批准的一款减肥处方药，作为一种辅助药物，联合低热量饮食和运动，用于肥胖成人患者的体重管理。

FDA非常关心Contrave可能的神经和心血管副作用。因此，仅批准Contrave用于体质指数(BMI)≥30（肥胖）的患者，以及体质指数（BMI）≥27（超重）且至少伴有一种体重相关的合并症（如高血压、2型糖尿病、高胆固醇（血脂异常））的患者群体。同时，FDA在Contrave药物标签中标注了一个可怕的“黑框”警告，告诫医生和患者，Contrave可能提高自杀念头及其他精神疾病的风险。另外，FDA已要求Orexigen开展上市后的安全性和有效性研究，包括在儿童患者群体和伴有肝肾疾病的成人患者群体。在FDA的规定中，“黑框”是置于处方药标识中最严重的一种警告，也意味着禁止药企直接对消费者进行广告宣传。

这些限制因素，可能会对Contrave如何在快速增长的肥胖症药物市场中立足形成严峻挑战。除了要与市面上Arena公司和卫材（Eisai）的减肥药Belviq及Vivus公司的减肥药Qsymia抗衡之外，Contrave也将很快面临诺和诺德减肥新药Saxenda的竞争。而诺和诺德也一直在扩大美国的销售队伍，为Saxenda的上市做积极准备，最最关键的是，Contrave很难挑战Saxenda在临床试验中的数据：在4项研究中，Saxenda治疗组有超过60%的患者体重降低5%，有近33%的患者体重降低超过10%。

而根据FDA的声明，Contrave的获批，是基于Orexigen公司整体临床试验数据包，其中包括采集自约4500例患者的数据，其中一项试验，Contrave治疗组有42%的患者体重降低至少5%，而安慰剂组患者比例为17%。

尽管面临诸多挑战，但华尔街分析师预计Contrave的最终销售额仍可能突破10亿美元。富国银行分析师预测，到2020年，Contrave的销售额可达到6.34亿美元，但如果FDA批准Contrave治疗糖尿病，那么Contrave的销售额将达到12亿美元。

然而，从已上市减肥药反响平平的市场接纳来看，摆在武田和Orexigen面前的困难仍然严峻。Belviq和Qsymia均于2012年上市，前者截至今年3月的销售额仅为2500万美元，后者在2013年的年销售额也仅为2370万美元。武田与Orexigen于2010年9月签署了Orexigen研发协议，双方共同负责药物在美国、加拿大、墨西哥的商业化。

英文原文：Takeda and Orexigen Announce Availability of CONTRAVE® (naltrexone HCI and bupropion HCI) Extended-Release Tablets for Chronic Weight Management in Obese Adults

Contrave is now available by prescription, and Contrave patients also have access to the Scale Down program and Direct Save to help support their complete approach to weight management

DEERFIELD, Ill. and OSAKA, Japan, Oct. 20, 2014 /PRNewswire/ -- Takeda Pharmaceutical Company Limited ("Takeda"), its wholly-owned subsidiary Takeda Pharmaceuticals U.S.A., Inc. and Orexigen® Therapeutics, Inc. (OREX) jointly announced today that Contrave® (naltrexone HCI and bupropion HCI) extended-release tablets are now available to patients by prescription in pharmacies across the United States. Contrave is approved by the U.S. Food and Drug Administration (FDA) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus or dyslipidemia).
6 c# b$ n8 L, o) C7 Q# i# Y"We're excited that Contrave is now available and that we are able to provide eligible patients with additional offerings," said Douglas Cole, president, Takeda Pharmaceuticals U.S.A., Inc. "These offerings include the Scale Down program, a support program for weight management, and Contrave Direct Save, which helps eligible patients to get Contrave at the lowest cost available to them, which can help to support a patient's complete approach to weight management."

Eligible patients taking Contrave will have access to the Scale Down program, which provides mobile weight management support with a wireless scale that triggers daily personalized texts based on weigh-ins. Scale Down, LLC is a company that is independent from Takeda and is solely responsible for the program content. Takeda will cover the membership costs associated with the Scale Down program for all eligible patients during the offer period.

In addition, eligible patients will have access to Contrave Direct Save, which provides the lowest cost available for both commercially insured and cash-paying patients, with one-on-one pharmacy support and the convenience of home delivery. When patients use the available savings offer, Contrave Direct Save provides progressive savings that begin on the third consecutive month of treatment if patients do not miss a refill. In addition to the Contrave Direct Save program, savings are also available to eligible patients through a Pharmacy Savings Card for those who prefer a retail pharmacy option.

Additional details about Contrave and the accompanying support and savings programs are available at www.Contrave.com/FAQ.

"Today is an exciting day for our team at Orexigen and our colleagues at Takeda as Contrave is now launched and available by prescription in pharmacies across the country," said Michael Narachi, CEO of Orexigen. "We're proud of our efforts working together to make this product available as a treatment option for appropriate patients."

Takeda and Orexigen entered into a collaboration agreement on September 1, 2010 for the development and commercialization of Contrave in the United States, Canada and Mexico. Under the terms of the agreement, Orexigen and Takeda agreed to work together on ongoing development of Contrave. Orexigen agreed to lead pre-approval development activities, and Takeda agreed to lead post-approval development activities. Orexigen originally submitted the New Drug Application (NDA) for Contrave to the FDA, which NDA was transferred to Takeda by Orexigen after Contrave was approved by the FDA on September 10, 2014.

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FDA专家委员会全票通过诺华牛皮癣药物secukinumab审核

                               
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发布日期：2014-10-22  来源：生物谷  浏览次数：14

本周，美国FDA下属的专家评审委员会全票通过了对secukinumab的审核，建议FDA正式批准其上市。
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在即将过去的十月份里，诺华公司可谓好消息不断。先是公司开发的CAR-T肿瘤疗法取得积极进展，然后是公司开发的治疗牛皮癣药物secukinumab临床三期研究取得重大进展。本周，美国FDA下属的专家评审委员会全票通过了对secukinumab的审核，建议FDA正式批准其上市。一般而言，经过这一委员会批准的药物最终都会被FDA批准进入市场销售。这也意味着，诺华公司已经扫除了secukinumab上市的最后一个障碍。FDA预计将于明年一月份正式决定是否允许secukinumab上市。

诺华公司开发的药物secukinumab是一种通过特异性阻断IL-17治疗牛皮癣的注射用蛋白药物。而一旦FDA批准其上市，secukinumab就将成为治疗牛皮癣类药物市场中第一个IL-17阻断剂药物。目前，牛皮癣市场上的主要产品都是TNF抑制剂类药物。

诺华公司对这一产品寄予厚望。公司高层相信这secukinumab一旦进入市场将极大地改变市场格局。举例来说，根据相关市场调查公司的分析报告显示，52％的牛皮癣患者对市场上现有药物的疗效不满，消费者希望能出现更有效的药物产品。而此前secukinumab在临床三期研究中，击败了安进公司治疗牛皮癣的明星药物Enbrel（同样是抗TNF药物，2013年销售额达到88亿美元）也给诺华公司以更大的野心和底气。

不过也有分析人士在此前就指出，诺华公司的secukinumab并非稳操胜券，因为多家生物医药巨头都已经对这一市场虎视眈眈。如强生、默沙东等公司都正在开发自己的治疗牛皮癣药物。因此，这场牛皮癣市场的竞争，究竟鹿死谁手还需要时间的检验。

详细英文报道：

A panel of FDA advisers voted unanimously in favor of approving Novartis' ($NVS) new anti-inflammatory treatment, an expected positive outcome for the company as it races to be first in line among what promises to be a crowded field.

Novartis' treatment, secukinumab, is an injected antibody that blocks interleukin-17, a protein that plays a major role in inflammation. The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee voted 7-0 that the company's pivotal data support the approval of secukinumab to treat plaque psoriasis, the first of Novartis' desired indications.

The FDA isn't beholden to follow the whims of its advisers, though it commonly does, and the agency is due to hand down a final decision on secukinumab's future in psoriasis in January.

If Novartis' drug wins approval, it'll be the first IL-17 blocker to hit the market, leading a pack of new treatments that could improve the standard of care for psoriasis, psoriatic arthritis and other inflammatory diseases.

Currently, the most common option for psoriasis sufferers are injected therapies that inhibit tumor necrosis factor (TNF), treatments that have brought in blockbuster sales. But Novartis believes its contender can disrupt the market, pointing to a National Psoriasis Foundation survey in which 52% of patients surveyed said they were dissatisfied with their disease management. And the company has plenty of data to back up its case for secukinumab, including results from a Phase III psoriasis trial in which the treatment beat out Amgen's ($AMGN) Enbrel, an anti-TNF drug that brought in about $8.8 billion last year.

"We are pleased with today's unanimous recommendation, which is based on the efficacy and safety data put forth in our robust clinical trial program, and the advisory committee decision brings us one step closer to delivering an innovative, new treatment option for people suffering from moderate-to-severe psoriasis," Novartis Global Head of Development Vas Narasimhan said in a statement. "There is a need for novel therapies, as not all treatments are appropriate or effective in every patient."

But while Novartis will likely be first to the IL-17 market, it's soon to be joined by a slew of other anti-inflammatory biologics targeting the same multibillion-dollar space. Behind secukinumab is Amgen and AstraZeneca's ($AZN) brodalumab, a similar treatment that has notched impressive Phase III results in psoriasis and psoriatic arthritis. Meanwhile, Eli Lilly ($LLY) is in the midst of Phase III with the IL-17-blocking ixekizumab, trailed by Merck's ($MRK) MK-3222 and Johnson & Johnson's ($JNJ) IL-23 inhibitor guselkumab, which is set to enter Phase III this quarter.

Novartis has psoriatic arthritis ambitions of its own, last month unveiling results from two Phase III trials in which secukinumab relieved symptoms of that disease, preventing joint damage and helping to maintain clear skin. Beyond the two leading indications, secukinumab is also in development for ankylosing spondylitis and rheumatoid arthritis, with filings for those conditions expected next year.

If the company can pull off all four approvals for its antibody, analysts have speculated that the drug could clear $1 billion in annual sales by 2020.

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拜耳Eylea糖尿病性黄斑水肿疗效击败Lucentis和Avastin

                               
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发布日期：2014-10-22  来源：生物谷  

Eylea于今年7月获欧美批准DME适应症，该项疗效比较研究，Eylea击败Lucentis和Avastin，使得Eylea在DME领域更具影响力。

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在一项由美国政府（NIH）资助的独立研究中，用于糖尿病性黄斑水肿（DME）治疗时，拜耳（Bayer）眼科药物Eylea击败了来自竞争对手诺华和罗氏的2种药物Lucentis和安维汀（Avastin）。Avastin是一种抗癌药物，但因价格优势常常标签外用药用于糖尿病性黄斑水肿（DME）的治疗。

在这项为期52周涉及660例DME患者的临床研究中，Eylea不仅在疗效上击败了Lucentis和Avastin，同时也取得了较好的安全记录，而且平均注射次数更少。RBC资本市场分析师认为，如果这些数据在明年的最终研究结果中得到证实，Eylea的优势将得到更大的提升。分析师引述StreetInsider，如果这些差距能够在第二年得以维持，Eylea在DME领域将更加具有影响力。

这对于拜耳和Regeneron来说，是一个大好消息。Eylea于2014年7-8月获FDA和欧盟批准用于糖尿病性黄斑水肿（DME）适应症。而诺华和罗氏眼科药物Lucentis分别于2011年和2012年获欧盟的FDA批准用于DME适应症。在DME治疗领域，Eylea正在努力追赶Lucentis。

不过，Eylea自2011年上市后，新适应症个数和全球销售额一直在不断刷新，数度超过业界预期。Eylea上市1年，在美国的销售额达到8.38亿美元；而在最近，今年第二季度，Eylea的表现再次超出业界预期，销售额达4.15亿美元，比去年同期增长26%。

政府资助的疗效比较独立研究：

该项研究是一项由美国政府资助的独立研究，目的是确定3种不同的抗VEGF疗法（Eylea，Avastin，Lucentis），在治疗糖尿病性黄斑水肿（DME）方面，是否其中一种药物优于其他2种药物。

该研究是一项疗效比较研究，由美国国立卫生研究院（NIH）赞助、糖尿病性视网膜变性临床研究网络（DRCR.net）领导，在660例糖尿病性视网膜病变（DME）患者中开展，数据表明，在研究的52周，与罗氏安维汀（Avastin，通用名：bevacizumab，贝伐单抗）和诺华/罗氏Lucentis（通用名：ranibizumab，兰尼单抗）相比，Eylea（aflibercept）使最佳矫正视力（BCVA）从基线水平取得了显著更大程度的改善，达到了研究的主要终点。此外，根据临床研究协议规定的复治方案（retreatment regimen），Eylea治疗组比Avastin和Lucentis治疗组注射次数少一个；同时，与Avastin和Lucentis治疗组相比，Eylea治疗组有较少的患者接受黄斑部位激光治疗。研究中，大部分眼部和全身不良事件（AEs）发生率在3个治疗组相似。

DRCR.net已将该研究的顶线数据与研究者分享，目前正在准备提交发表并计划在未来的医疗会议公布详细数据。在发表之前，DRCR.net暂时不会公布结果。该项研究的数据，将为临床视网膜专家及其患者，提供非常有用的信息，帮助指导治疗决策。该项研究的协议细节可在www.drcr.net上找到。

英文原文：Regeneron's Eylea bests Lucentis, Avastin in diabetic eye disease, NIH study finds

Regeneron and Bayer's Eylea hasn't had any trouble hanging with rivals from Novartis ($NVS) and Roche ($RHHBY), racking up sales that have consistently topped analyst expectations since its U.S. rollout in late 2011. Now, new data may help it potentially top them in a market the Swiss drugmakers got to first.

On Friday, Regeneron ($REGN) announced that in an NIH-sponsored study, Eylea bested both Lucentis and Avastin--a cancer drug that docs often use off-label, thanks to its significantly lower price tag--at treating diabetic macular edema (DME).

Not only did Eylea win out efficacy-wise after 52 weeks, but it also posted a better safety record and required fewer injections on average--advantages that could provide an even bigger boost if they're confirmed by final study results due next year, according to RBC Capital Markets analyst Adnan Butt.

If anything, the data "help Eylea's launch in DME, with the potential to be even more impactful if differences persist at two years," he said, as quoted by StreetInsider.

That's good news for Bayer and Regeneron, who will be playing catch-up in DME. Roche ($RHHBY) and Novartis ($NVS) picked up nods for the malady in Europe and the U.S. in 2011 and 2012, respectively.

But it's not like playing catch-up has been a problem for Eylea's marketers so far. After racking up $838 million in U.S. sales in its first full year on the market, the drug has gone on to trounce one analyst estimate after the next. Most recently, it netted $415 million in second-quarter sales for Tarrytown, NY-based Regeneron, a 26% leap over the year-ago period.

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