据介绍，对埃博拉病毒的研究始于2001年“911事件”后，因为担心埃博拉病毒会被用于生物恐怖武器，所以美国、加拿大等国家都投入了一定的经费用于埃博拉病毒的疫苗和治疗等医学研究。
其中，一种以VSV的病毒作为载体的DNA疫苗显现了初步的效果。VSV病毒是一种对人无害，而又能在体内持续复制和存活的病毒。科研人员将VSV病毒表达外壳蛋白的基因片段替换成埃博拉病毒外壳蛋白的基因片段后，将该病毒转染到小鼠、豚鼠和猴子体内，均产生了一定的保护效果，而且转染方式并不局限于肌肉注射，口服、鼻腔喷雾都有效。但这种VSV载体的疫苗只能用于感染埃博拉病毒前的预防，感染埃博拉病毒后，哪怕只是30分钟，疫苗就失去了作用。邱博士等人又将研究的重点转向了治疗。
病毒感染最有效的方法往往是用该病毒的中和抗体。历史上，用恢复期病人的血清或体液中的抗体治疗病毒感染，屡试不爽。名医孙思邈就曾用取自天花口疮中的脓液敷着在皮肤上来预防天花。非典的时候，也做过这种尝试。治疗用的狂犬病免疫球蛋白就是用狂犬病疫苗免疫的献血员提供的血浆或者是马血清制备的。
对于埃博拉病毒，无论是恢复期病人的血清，还是免疫后的马血清，似乎都没有治疗的作用。2007年，邱博士所在团队的研究在制备出8种鼠的单克隆抗体后，陷入了停顿。一方面是因为投资方失去了资助的热情，另一方面在等待专利的审批。直到2010年，科学家发现，精制纯化后的埃博拉抗体确有治疗的作用，投资方才又不遗余力地资助起邱博士的单克隆抗体研究。
首先是分别测试这8种单克隆抗体的治疗作用。邱博士用LD50(半数致死量，能杀死一半试验总体的有害物质、有毒物质或游离辐射的剂量)的1000倍来给小鼠染毒，这是肯定能杀死小鼠的剂量。染毒后24小时内注射单克隆抗体，小鼠都存活了下来。时间再长，48小时，7种抗体还有效；72小时，只有1种抗体有效。邱博士又开始尝试用豚鼠，24小时，8种抗体都有效；48小时抗体的“能力”开始出现明显分化，有的活了下来；再长，抗体的作用越来越弱。这样的抗体肯定是不能用于治疗的。
用一种抗体不行，用几种抗体组合呢？邱博士选择了3种作用最好的单克隆抗体组成的“鸡尾酒”，又开始了研究。这一次，将染毒后的时间延长到了48小时，存活率达到了50%以上，似乎已是“鸡尾酒”抗体的极限。而埃博拉病毒在人体的潜伏期是3-21天，这意味着“鸡尾酒”抗体至少要能在染毒72小时之后还能发挥作用才行。
“他山之石可以攻玉。”邱博士想到了另外公司的产品——一种能产生人干扰素的病毒作为“鸡尾酒”抗体的佐剂。干扰素是一种广谱抗病毒剂，是机体杀死病毒的“万金油”。不出意料，添加佐剂的“鸡尾酒”抗体果然为染毒72小时的恒河猴产生了100%的治疗作用。文章发表在2013年10月的《科学·转化医学》杂志上。邱博士不无遗憾的说，本来这篇文章想发表在影响力更高的杂志，但在同行评议时，一位同行专家指出对照数太少而被拒稿。此时，西非埃博拉疫情还没有发生。
不到一年后，埃博拉病毒造成了两千多人感染，一千多人丧生，分别超过了1976年发现埃博拉病毒到2011年感染和死亡人数的总和。邱博士的同事也有三人受命赴西非给予技术援助。临行时，为防止万一，同事带上了一剂“鸡尾酒”抗体。正是这一剂药，救了美国医生33岁的布兰特利一命(科学网，冒险一博：新药可能救活了美国埃博拉病毒(Ebola)患者)。
研究继续进行。邱博士所在的加拿大公共卫生署与美国部队医学研究所合作，共享了各自研制的单克隆抗体，通过试验、选择了最优的抗体组合“ZMapp”。近期在《Nature》杂志网站刊载的文章即染毒后3、4、5天的恒河猴用ZMapp治疗试验。
邱博士说，两国合作的ZMapp试验结果远超出了她的50%治愈率的预期。她还介绍了试验中的一个小插曲：按加拿大动物保护的规定，在试验过程中也要给受试动物健康状况评分，当动物健康状况低于一定程度时就要及时处死动物，减少动物受苦。在染毒后第4天时，有两只猴埃博拉病毒感染的症状开始加重。而按计划，这组的6只猴要在第5天才能接受首次ZMapp注射。第5天，动物管理员又对这组的猴做了一次健康状况评分，仍未达到处死标准，于是给予了ZMapp注射。很快，埃博拉病毒感染症状消退了。试验最终获得了100%治愈率。
最后，邱博士还介绍了ZMapp的人源化改造进展。她说，加拿大研制的单克隆抗体人源化改造已经完成，并交由生物公司开始进行批量生产。美国的单克隆抗体人源化改造还在进行中，一旦完成改造和批量生产，就可以开展进一步的效能试验。
尽管到临床的应用还需要一段时间，邱博士表示对单克隆抗体治愈埃博拉病毒感染“很有信心”，因为动物试验中的小插曲已经显现了ZMapp抗体强大的逆转病程的作用。
5、默克Keytruda（pembrolizumab）成为FDA批准的首例PD-1单抗 发布日期：2014-09-05 来源：fiercebiotech
美国默克9月4日宣布，公司旗下Keytruda（pembrolizumab）正式成为美国食品药品监督管理局（FDA）批准的首例PD-1单抗。该药适应症为不可切除的或转移性黑色素瘤。
Pembrolizumab是一种新型人源化单抗，通过作用于程序性细胞死亡1（PD - 1的）提升人体免疫力，消灭晚期黑色素瘤。根据临床I期数据显示，24%黑色素瘤患者在接受治疗之后体内的肿瘤大小出现缩小。
默克正在进行晚期黑色素瘤的临床II期研究和临床III期研究，为该药物提供进一步研究支持。公司计划在未来一周内正式上市Pembrolizumab。
Keytruda 是阻断 PD-1 细胞通路的首款获得批准的药物，PD-1 可限制人体免疫系统攻击黑色素瘤细胞。Keytruda 供伊匹单抗治疗后使用，伊匹单抗也是一种免疫治疗药物。
“Keytruda 是自 2011 年以来获得批准的第六款黑色素瘤治疗药物，这是黑色素瘤研究取得良好进展的一个结果，”FDA 药物评价与研究中心血液及肿瘤产品办公室主任、医学博士 Pazdur 称。“这些药物中好多有不同的作用机制，为黑色素瘤患者带来新的治疗选择。”
FDA 之前批准的五款黑色素瘤药物有伊匹单抗 (2011)、聚乙二醇化干扰素α-2b(2011)、威罗菲尼(2011)、达拉菲尼(2013) 和曲美替尼(2013)。
FDA 授予了 Keytruda 突破性治疗药物资格，因为申请者通过初步临床证据证明这款药物可以提供与现有治疗药物相比的实质性进展。这款药物还获得优先审评资格及孤儿药资格。优先审评资格授予在上市申请提交时有潜力在严重疾病治疗中对安全性或有效性有明显改善的药物。孤儿药资格授予旨在治疗罕见疾病的药物。
FDA 对 Keytruda 的批准是按加速批准计划进行的。这一计划可以让患者更早地获取有前景的新药，同时制药公司要进行验证性临床试验，因为在生存期或疾病相关症状方面的改善尚未确定。
Keytruda 的疗效基于 173 名经过之前治疗后疾病又恶化的晚期黑色素瘤临床试验受试者。所有受试者均以 Keytruda 治疗，用药剂量为 2mg/kg 或更高剂量 10 mg/kg。有一半受试者接受推荐剂量 2mg/kg 治疗，其中大约 24% 的患者肿瘤缩小。这种效果持续了至少 1.4 至 8.5 个月，而在大多数患者中，这种效果的持续时间超过了这一周期。以 10mg/kg 剂量接受治疗的患者中，有类似比例的患者其肿瘤出现缩小。
Keytruda 的安全性基于由 411 名晚期黑色素瘤患者参与的临床试验。Keytruda 最常见的副作用有疲劳、咳嗽、恶心、皮肤瘙痒、皮疹、食欲下降、便秘、关节疼痛 (关节痛) 和腹泻。Keytruda 还可能有严重免疫介导副作用。在 411 名晚期黑色素瘤受试者中，涉及健康器官（包括肺、结肠、产生激素的腺体及肝脏）的严重免疫介导副作用的发生极其罕见。 Keytruda 由位于新泽西州怀特豪斯的默沙东上市销售。
Merck wins breakthrough FDA approval for blockbuster cancer contender pembrolizumab
Merck ($MRK) has won the frenzied race to secure the first FDA approval for a new breed of cancer treatment, clearing the way for a U.S. launch and a scramble for dominance in a field expected to peak at nearly $35 billion a year.
The agency has signed off on Merck's pembrolizumab (formerly MK-3475) for melanoma, the first of the company's many planned indications. The drug is designed to galvanize an immune system attack on tumors by blocking a pathway called PD-1, which, left unchecked, allows cancerous cells to pass undetected. The approval, handed down almost two months ahead of schedule, clears the drug for use on patients with advanced skin cancers who have already taken Bristol-Myers Squibb's ($BMY) Yervoy (ipilimumab).
With the victory, Merck becomes the first mover in a blockbuster race to commercialize a PD-1 treatment in the U.S., beating out rivals Bristol-Myers, AstraZeneca ($AZN) and Roche ($RHHBY), among others. Pembrolizumab, which will sell as Keytruda, is the second such therapy to win approval around the world, following last month's Japanese OK for nivolumab from Bristol-Myers and partner Ono Pharmaceutical.
It won't be cheap. The cost for this drug will be $12,500 a month, or $150,000 a year, the low end of the ambitious range expected by Bernstein's Tim Anderson. That puts pembrolizumab on track to earn $3.5 billion a year, according to Anderson, which would make this treatment the first bone fide blockbuster to come out of Merck's pipeline in years. Nivolumab from Bristol-Myers Squibb is still tapped by the analyst as the likely overall market winner, with $4.4 billion in expected peak sales. And Roche and AstraZeneca complete the top four group in immuno-oncology, with potential sales of $3.8 billion and $1.4 billion for their rival programs.
The biggest promise for PD-1 blockers--both clinically and commercially--likely lies in combination therapies, and Merck has launched a fleet of cocktail studies that match pembrolizumab with treatments from Pfizer ($PFE), Amgen ($AMGN), Incyte ($INCY) and others in hopes of bolstering the drug's stirring potential as a monotherapy. Its competitors have followed suit, and the coming years are likely to see a host of PD-1 treatments approved for use in tandem with other therapies in a variety of cancers.
In the near term, Bristol-Myers is closest on Merck's heels in the U.S., planning to submit its PD-1 candidate for FDA scrutiny next quarter. Roche and AstraZeneca are not far behind with their contenders, and each company is banking on the agency following through on its promise of swift reviews for the breakthrough class of therapies.
For Merck, the drug is the star of refocused and revamped pipeline. Under the direction of R&D chief Roger Perlmutter, the once-sluggish pharma giant has ditched programs and slashed jobs in an effort to pare down and invest in high-potential candidates, and pembrolizumab is its first major regulatory victory since Perlmutter took over last year.
"Keytruda embodies Merck's unwavering commitment to pursue breakthrough science to help people who are facing the most challenging diseases," CEO Kenneth Frazier said in a statement.
Pembrolizumab's nod marks the 6th approval for a melanoma treatment since 2011, according to the FDA, reflecting both the explosion of research advances in the field and the series of the disease. Melanoma accounts for about 5% of all new cancers in the U.S., the agency said, killing nearly 10,000 people each year.
6、默克抗生素新药Relebactam（MK-7655）进入FDA快速审批通道 发布日期：2014-09-05 来源：dddmag
美国默克9月4日宣布，公司旗下新药Relebactam（MK-7655）正式进入美国食品药品监督管理局FDA快速审批通道。该注射液可用于尿路感染、复杂腹腔感染和院内细菌性肺炎。
默克称，Relebactam同时获得合格传染病产品（QIDP）认证。该项认证旨在鼓励药企开发新型抗生素药物，激励措施内容包括产品专利延期5年以及快速审批通道。
Relebactam是一种实验性β-内酰胺酶抑制剂（beta-lactamase inhibitor ）。该注射液和亚胺培南/西司他丁联合用药正在进行临床II期试验。公司计划在2015年启动临床III期研究。
FDA Puts Merck's Relebactam on Fast Track as QIDP
Merck, known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has designated relebactam (previously known as MK-7655), the company’s investigational beta-lactamase inhibitor, as a Qualified Infectious Disease Product (QIDP) with designated Fast Track status. The QIDP and Fast Track designations apply to intravenous use of relebactam for the treatment of complicated urinary tract infections, complicated intra-abdominal infections and hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.
QIDP designation, provided under the Generating Antibiotic Incentives Now (GAIN) Act, offers certain incentives for the development of new antibiotics, including a five-year extension of the data exclusivity provisions under the Hatch-Waxman Act and priority review of the New Drug Application when filed. Fast Track designation provides for enhanced communication with the FDA during the drug development program.
“The lack of new medicines to fight drug-resistant infections is a growing public health concern,” said Dr. Nicholas Kartsonis, executive director, Infectious Disease, Merck Research Laboratories. “We are pleased that the FDA has designated relebactam as a QIDP with Fast Track status, and we look forward to working with the FDA and other experts in infectious disease to study this medicine with the goal of bringing it to people suffering from potentially life-threatening resistant bacterial infections as quickly as possible.”
Beta-lactamases are a family of enzymes produced by some bacteria that can cause resistance to several widely used beta-lactam antibiotics, including penicillins, cephalosporins and carbapenems. By combining a beta-lactamase inhibitor with a beta-lactam antibiotic, it may be possible to overcome the resistance and extend the spectrum of activity of the antibiotic to fight infections.
Relebactam is an investigational, class A and C, beta-lactamase inhibitor that is being evaluated in combination with imipenem/cilastatin in ongoing Phase 2 clinical trials for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. In preclinical studies, relebactam administered in combination with imipenem/cilastatin demonstrated antibacterial activity against a broad range of Gram-negative and beta-lactam-resistant pathogens. Merck plans to initiate Phase 3 studies with relebactam in combination with imipenem/cilastatin in 2015.
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