越来越多的迹象表明，新药上市速度可能要减缓，但英国要让新药加速上市。一项以税收为来源的基金专为那些还未通过英国国家临床规范研究院（NICE）审批的新药提供支付，让患者更早接受治疗。
Sovaldi是个例外？
Sovaldi在众多试验中被证明具有良好疗效，事实上，它是到目前为止治疗丙肝最有效的药物。最近的试验数据显示，Sovaldi可以在12周时间内治愈90%的丙肝病人，与Vertex的Incivek（telaprevir）和默沙东的Victrelis（boceprevir）相比，效果显著，后者的治疗时间是前者的两倍，治愈率只有75%。
Sovaldi的显著疗效为它带来了惊人的销售额，2014年第一季度销售额超过20亿美元，第二季度达32亿美元，是销售额增长最快的药物，照此趋势，明年销售额将突破100亿美元。
从理论来说，Sovaldi可以治愈所有类型的丙肝患者，让慢性丙肝患者免于肝移植和长期护理，将为NHS节约一大笔费用。而且，它还有众多支持者，尤其是一些丙肝患者组织，如制药企业赞助的英国丙肝基金会（the Hepatitis C Trust），正在积极呼吁基金支持该药的使用。
更重要的是，在2014年制药业信誉报告中，吉利德被评为第二大受人尊重的制药企业，排名在ViiV公司之后，后者是葛兰素史克和辉瑞的合资公司，也专注于传染性疾病的药物开发。
由此可见，吉利德还是受到了公众广泛的赞誉，无论是在公司信誉、治疗效果还是患者支持方面，没有任何一家公司拥有如此坚实的群众基础。
治愈率高花费也高
Sovaldi的定价充满争议，到目前为止，吉利德还无法说服美国人，为什么该药的日治疗费要100美元，一个疗程需要84000美元。
英国使用Sovaldi的费用要低得多，28片400mg的Sovaldi售价约为11661英镑，按此计算，12周的治疗费用约为34983英镑，与罗氏的注射剂Copegus联合用药还需加上2400英镑的费用。尽管如此，Sovaldi仍然是NHS目录中最贵的药品，甚至比很多治疗癌症的生物药还贵得多。
医疗技术人员对该药的评估反应不一。今年6月，苏格兰医药协会批准Sovaldi进入苏格兰NHS支付目录，用于1~6基因型丙肝治疗，但有一定的使用限制，比如基因2型患者仅在不能耐受Pegasys治疗时使用Sovaldi；基因3型患者采用24周无干扰素，“Sovaldi+Copegus”联合用药方案。
当然，NICE并未读过英格兰地区的NHS方案，也没有在6月第一次出版的指导草案中找到与Sovaldi成本效益相关的内容。NICE健康技术评估部负责人Carole Longson教授这样解释目前的暂行决定：“我们已经有足够证据证明，Sovaldi对某些丙肝患者极为有效，但于特殊基因型患者是否有效现在还缺乏证据，生产者也没有提供确切答案。”
该组织要求吉利德提供更多信息，尤其是“Sovaldi+ Copegus”与“Sovaldi+ Copegus+Pegasys”两种治疗方案治疗基因1型和基因3型丙肝患者的疗效对比；并将根据患者是否患有肝硬化、艾滋病或其他病史，进一步评估Sovaldi的成本效益，最终的评价结果将于今年底发布。
英格兰NHS表示，将在NICE指导性意见出台后，对目前的药品政策再作调整，但未明确如果NICE的治疗指南出不来，目前的资金支持还能维续多久。
一个新的CDF？
Sovaldi的资助方案容易与英国之前的CDF联系起来，该项基金投入2亿英磅，专为在2016年以前未能通过NICE审批或监管机构不批准的药物使用提供资金支持。对于这个由政府直接管理、只针对癌症用药的基金，不少人颇有微辞。NICE主席近日接受Pharmafocus采访时称，对CDF的政治性表示遗憾。
CDF基金始于2010年，将运行至2016年，截至目前花费已接近10亿美元。它确实让很多癌症患者获得了最新的抗肿瘤药治疗，但也让纳税人额外支付了一大笔开销。目前几乎没有证据支持它提高了癌症的临床收益，但政府在公众和媒体中赢得良好名声，也让英国的抗癌药研发企业大赚一笔（药品绕开NICE监管高价销售），受益企业包括罗氏、Celgene和默沙东等抗癌药大户。
NICE判断一个药物是否具有良好的成本效益通常需要6~9个月，在得到肯定结论后，该药将进入各地的NHS用药目录，并在3个月内进入临床。走完整个流程大概需要1年时间，但不是每一个晚期丙肝患者都能等这么久，无论是从政治还是临床治疗角度来看，提高NICE的效率至关重要，但NICE只是政府部门的一个分支，它不能自己作出决定。
问题在于，与Sovaldi类似的其他药物能否通过NICE批准？目前，杨森、安博维、默沙东和百时美施贵宝的丙肝治疗药物都处于后期研发阶段，疗效与Sovaldi类似甚至有所超越。这些药物在获得欧洲上市许可后、拿到NICE批准前，是不是也能获得类似Sovaldi的基金支持？显然，这是NHS无法承受的，事实上，Sovaldi是特定时期出现的特例，其他企业无法模仿，但不保证未来不会出现类似基金。
当年的CDF为癌症治疗带来希望，Sovaldi的出现也是一个为全球患者带来福音的伟大创新，不过一只药物的销量最终还是取决于它的临床疗效、信誉和公共支持工作。
加拿大批准Abraxane用于转移性胰腺癌的一线治疗 发布日期：2014-08-08 来源：新药汇
加拿大卫生部批准新基（Celgene）Abraxane联合吉西他滨用于转移性胰腺癌的一线治疗，此前该药已获FDA和欧盟批准用于晚期胰腺癌的治疗。
美国生物制药公司新基（Celgene）8月6日宣布，加拿大卫生部批准Abraxane（注射用紫杉醇[白蛋白结合型]）联合吉西他滨（gemcitabine），用于转移性胰腺癌成人患者的一线治疗。这是近20年来，加拿大批准的首个治疗转移性胰腺癌的药物。目前，Abraxane+吉西他滨联合疗法已获30多个国家批准，用于转移性胰腺癌的治疗，包括美国和欧盟。
迄今为止，吉西他滨作为胰腺癌的标准护理，已有超过15年的时间。而Abraxane+吉西他滨联合疗法，在临床试验中，已被证明对关键疗效终点表现出临床意义的显着改善，包括总生存期，同时具有良好的安全性，该联合疗法将为胰腺癌患者提供一个重要的新治疗选择，并为今后的临床研究奠定基础。
Abraxane的获批，是基于III期MPACT研究的数据。MPACT是一项开放标签、随机、国际性III期研究，研究中861例初治转移性胰腺癌患者随机接受ABRAXANE+吉西他滨联合疗法或吉西他滨单药疗法，研究数据表明，与吉西他滨单药疗法相比，ABRAXANE+吉西他滨联合疗法在总生存期（OS）、疾病无进展生存期（PFS）、整体响应率（ORR）上均表现出统计学意义的显着改善：OS（8.5个月 vs 6.7个月，HR=0.72，p＜0.0001），死亡风险降低28%；PFS（5.5个月 vs 3.7个月，HR=0.69，p＜0.0001），疾病进展或死亡风险降低31%；ORR（23% vs 7%，p＜0.0001）。
在过去的20年中，在晚期胰腺癌患者中开展了超过30项随机III期临床试验，MPACT研究是表现出总生存期（OS）利益的4项研究之一。
关于胰腺癌：
胰腺癌是全球第8大癌症死因。胰腺主要由2种细胞类型组成：外分泌和内分泌。外分泌肿瘤是目前最常见的一种胰腺癌，恶性腺瘤占胰腺癌症的95%。在加拿大，对于各阶段的胰腺癌患者群体，5年存活率约为8%；而对于转移性胰腺癌而言，5年存活率约为2%。
关于Abraxane：
Abraxane是紫杉醇的白蛋白结合形式，采用nab专利技术生产。Abraxane的配方中含有白蛋白，白蛋白是一种人源性蛋白质，Abraxane的配方中不含溶剂。
Abraxane于2005年1月在美国首先获准用于治疗联合化疗无效的转移性乳腺癌或辅助化疗6个月内复发的乳腺癌 。既往治疗必须包含一种蒽环类，除非有临床禁忌症。Abraxane还在下列地区获准用于治疗转移性乳腺癌：加拿大、印度、欧盟/欧洲经济区(EU/EEA)、韩国、中国、澳大利亚、不丹、阿联酋、尼泊尔、新西兰、日本、俄罗斯、斯里兰卡和阿根廷。
2012年10月，美国FDA批准Abraxane联合卡铂用于不适合治愈性手术或放疗的局部晚期或转移性非小细胞肺癌的一线治疗。此外，Abraxane也获日本和阿根廷获准用于非小细胞肺癌的治疗，并且还在日本获准用于胃癌的治疗。
Abraxane目前处于不同的研究阶段，用于下列癌症的潜在治疗：黑色素瘤、膀胱癌、卵巢癌以及乳腺癌、肺癌的扩展应用。
英文原文：Health Canada Approves ABRAXANE® Plus Gemcitabine for First-Line Treatment of Patients with metastatic Pancreatic Cancer
High unmet need addressed with first new approved treatment in eighteen years
MISSISSAUGA, ON, August 6, 2014 /CNW/ - Health Canada has approved PrABRAXANE® for Injectable Suspension (paclitaxel powder for injectable suspension) (nanoparticle, albumin-bound [nab®] paclitaxel) for first-line treatment of adult patients with metastatic pancreatic cancer. The approval is welcome news for Canadians who are diagnosed with metastatic pancreatic cancer, and represents the first approved treatment for this disease in nearly two decades.
The Health Canada approval was based on the results of MPACT (metastatic Pancreatic Adenocarcinoma Clinical Trial), an open-label, phase III, randomized, international study which was published in the New England Journal of Medicine in October 2013. The MPACT study involved 861 chemotherapy-naïve patients with metastatic pancreatic cancer from 11 countries, including Canada, and showed a statistically significant improvement in median overall survival with ABRAXANE plus gemcitabine compared to gemcitabine alone (8.5 vs. 6.7 months) (HR 0.72, P1
"This is a cancer wher there are few effective treatments and the first-line approval of ABRAXANE in combination with gemcitabine represents an important advance," said. Dr. Malcolm J. Moore, Program Head, Medical oncology and Hematology and Director, McCain Centre for Pancreatic Cancer at the Princess Margaret Cancer Centre, University Health Network in Toronto and an investigator in the MPACT trial. "This approval will certainly have an impact on the way physicians manage this disease in the future. Pancreatic cancer is a tough one to deal with; patients are desperate and physicians are on the lookout for new advances. The addition of ABRAXANE to gemcitabine has demonstrated significant benefits in overall survival and this gives our patients hope."
"It's been quite some time since we've seen any type of treatment advance for pancreatic cancer making this news so important for patients. This will give patients the hope that is needed to continue to fight," said Laurie Ellies, Co-founder, and Acting Executive Director of Pancreatic Cancer Canada. "Over the past decade, there has been a significant improvement in cancer survival rates. Sadly, the same cannot be said about pancreatic cancer. We're dealing with a deadly disease. For a person diagnosed with metastatic disease it can be a question of weeks. This year alone, we can expect an estimated 4,700 Canadians will be diagnosed with this disease. If anything, this number tells us that we are desperately in need of more research and treatments - patients are counting on it."
ABRAXANE is commercially available in Canada.
about Pancreatic Cancer
Pancreatic cancer is the fourth-leading cause of cancer-related death in Canada.2 The pancreas is composed of two main cell types: exocrine and endocrine. Adenocarcinoma is a sub-type of exocrine tumors and accounts for about 95% of cancers of the pancreas.3 For all stages of pancreatic cancer combined, the five-year survival rate in Canada is about 8%. For metastatic pancreatic cancer, the five-year survival is approximately 2% in Canada.2
about ABRAXANE®
ABRAXANE® is an albumin-bound form of paclitaxel that is manufactured using patented nab® technology. ABRAXANE is formulated with albumin, a human protein, and is free of solvents. The most common adverse reactions (≥ 20%) with a ≥ 5% higher incidence in the ABRAXANE/gemcitabine treatment group are neutropenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, decreased appetite, rash, and dehydration.4
Please refer to the ABRAXANE product monograph for complete safety information.
ABRAXANE in combination with gemcitabine for the treatment of metastatic pancreatic cancer is approved in the United States and 30 other countries, including Argentina and Australia as well as countries in Europe.
FDA授予Genoa制药GP-101（吡非尼酮气雾剂）孤儿药地位 发布日期：2014-08-08 来源：新药汇
FDA授予Genoa制药公司GP-101(吡非尼酮气雾剂)治疗特发性肺纤维化（IPF）的孤儿药地位。
Genoa制药8月6日宣布，FDA已授予GP-101（吡非尼酮气雾剂，aerosol pirfenidone）治疗特发性肺纤维化（IPF）的孤儿药地位。
口服吡非尼酮（品牌名Esbriet）已被证明能够减缓IPF病情的恶化。然而不幸的是，需要非常大的口服剂量才能够实现有效的肺部药物浓度。尽管已确立了吡非尼酮的上限安全阈值（801mg TID，即：801毫克，每天3次），但通过口服给药所能递送的肺部剂量太低，而不能实现最佳的疗效。此外，口服吡非尼酮后的胃肠暴露及其血液水平的耐受性很差。由于这些原因，通过提高口服剂量来获得最佳IPF治疗效果是不可能实现的。此外，还有其他一些复杂的问题，如食物对药物的吸收、首过代谢、安全性所致的剂量减少、停药方案等，进一步降低了药物的肺部剂量以及维持治疗的中断。
为解决口服的缺点并使IPF疗效最大化，Genoa公司对吡非尼酮的配方进行了改造，开发了一种新颖的吸入性吡非尼酮（GP-101），能够产生吡非尼酮气雾剂并将其直接递送至肺部。通过这种方法，非常小剂量的吸入性吡非尼酮便可实现与口服吡非尼酮（Esbriet）相当的IPF疗效（5mg vs 801mg，剂量降低160倍）。鉴于如此小的吸入性剂量，口服吡非尼酮时存在的安全性和耐受性问题便迎刃而解，从而提高患者的依从性，并有望提高吸入性剂量实现优越的IPF疗效。除了作为一种疗效改善的Esbriet替代品，GP-101作为一种安全和良好耐受性的吸入性产品，有望与其他药物（如勃林格殷格翰的IPF新药nintedanib）联合用药。
特发性肺纤维化（IPF）是一种常见的特发弥漫性肺纤维化疾病,是慢性非肿瘤呼吸系统疾病中预后最差的一种疾病。其主要症状是进展性呼吸困难和肺功能不可逆损害。许多患者以渐进性呼吸急促,躯体残疾,急性恶化为发病特征,确诊数年内患者就可能会死亡,死亡率甚至高于许多癌症。很显然,改善呼吸质量,提高存活期是目前此病的主要治疗目标。
英文原文：Genoa Pharmaceuticals Receives Orphan-Drug Designation for Pirfenidone in the Inhaled Treatment of Idiopathic Pulmonary Fibrosis (IPF)
San Diego, CA – August 5, 2014 – Genoa Pharmaceuticals, the leader in inhaled medicines for pulmonary fibrosis, today announced the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to Genoa for the use of pirfenidone in their lead program – inhaled GP-101 for the treatment of IPF.
"Acquiring orphan status marks an important regulatory milestone in GP-101’s life cycle to treat people with this devastating disease,” said Mark Surber, Ph.D., Genoa’s President and Chief Executive Officer. "We are pleased to continue the development of inhaled GP-101, with clinical trials beginning in early 2015."
Oral pirfenidone (Esbriet®) has shown promise to slow IPF disease progression. Unfortunately, a very large oral dose is required to achieve efficacious lung levels. Despite being established at the upper safety threshold (801 mg TID), the resulting oral-delivered lung dose is too low for optimal effect. Moreover, gastrointestinal exposure and large-associated blood levels remain poorly tolerated. For these reasons oral-dose escalation for optimal IPF efficacy is not possible. Complicating matters, dose-absorbing food, first-pass metabolism, and safety-driven dose-reduction and stoppage protocols further reduce lung dose and interrupt maintenance therapy.
To address oral shortcomings and maximize IPF efficacy, Genoa has reformulated pirfenidone for aerosol formation and inhaled, direct-lung delivery (GP-101). By this approach, ~160-fold less inhaled pirfenidone is predicted to deliver Esbriet-equivalent IPF efficacy (5 mg vs. 801 mg). With such a small inhaled dose, remaining safety and tolerability concerns may be eliminated, enabling improved patient compliance and an increased inhaled dose for superior IPF efficacy. In addition to serving as an improved-effect Esbriet replacement, a safe and well-tolerated inhaled product is expected to enable desired, but otherwise poorly-tolerated combination regimens (e.g., with Boehringer Ingelheim’s Nintedanib).
about Orphan Drug Designation
Orphan drug designation is a status assigned to a medicine intended for use in rare diseases. In the U.S., the Orphan Drug Designation program provides orphan status to medicines intended for the safe and effective treatment or prevention of rare diseases that affect fewer than 200,000 people. In the E.U., a medicine must meet similar criteria, affecting up to five in 10,000 people. Orphan designation for inhaled GP-101 will be pursued in the E.U. with clinical data. Orphan status provides sponsors with development and commercial incentives, including 7 and 10 years market exclusivity for these two regions, respectively.
about IPF
IPF is a fatal lung disease caused by both genetic and environmental factors resulting in progressive lung scarring and death due to respiratory failure and/or co-morbidities. Characterized by a dry cough, shortness of breath and decreased exercise capacity, this disease exhibits a post-diagnosis survival period of ~2-5 years, annually killing more people than breast cancer. As fibrosis is at present irreversible, an efficacious product will provide a well-tolerated stand-alone or combination maintenance therapy that protects healthy lung tissue against invading fibrosis or meaningfully slows disease progression.
about Genoa Pharmaceuticals
Genoa Pharmaceuticals, Inc. is committed to developing improved therapies for the treatment of IPF. based in San Diego, Genoa’s lead program, GP-101 (aerosol pirfenidone) plans to enter clinical trials in early 2015.
FDA授予百特pacritinib快车道地位 发布日期：2014-08-08 来源：新药汇
FDA授予百特骨髓纤维化药物pacritinib快车道地位，该药是一种口服酪氨酸激酶抑制剂，具有针对JAK2和FLT3的双重活性。与当前其他JAK抑制剂相比，该药具有很大的优势。
百特国际（Baxter International）和合作伙伴CTI生物制药公司8月7日联合宣布，FDA已授予pacritinib快车道地位，用于治疗中危及高危骨髓纤维化（myelofibrosis，MF），包括但不限于伴有血小板减少症的患者、正经历其他JAK2疗法出现血小板减少症的患者、以及对其他JAK2疗法不耐受或其症状经其他JAK2疗法管理不佳的患者。目前，pacritinib正处于2个III期临床（即PERSIST项目），评估用于骨髓纤维化患者的治疗。
Pacritinib是一种口服酪氨酸激酶抑制剂，具有针对JAK2和FLT3的双重活性。JAK激酶家族是信号传导通路的重要组成部分，对于正常血细胞的生长和发育、炎性细胞因子的表达、免疫反应至关重要。已有研究表明，这些激酶的突变与各类血液相关癌症的形成直接相关，包括骨髓增生性肿瘤、白血病和淋巴瘤。Pacritinib能够有效治疗疾病症状，同时具有更少的药物出现的血小板减少症及贫血，这些副作用常见于目前已获批及在研的JAK抑制剂；因此，与其他JAK抑制剂相比，pacritinib具有很大的优势。
骨髓纤维化（myelofibrosis，MF）简称髓纤，是一种由于骨髓造血组织中胶原增生，其纤维组织严重地影响造血功能所引起的一种骨髓增生性疾病。骨髓纤维化是由恶性骨髓细胞的积累所致，触发炎症反应，使骨髓形成瘢痕，限制骨髓产生红细胞的能力，并促使脾脏和肝脏接管造血功能。该病具有不同程度的骨髓纤维组织增生，以及主要发生在脾、其次在肝和淋巴结内的髓外造血，典型的临床表现为幼红细胞及幼粒细胞性贫血，并有较多的泪滴状红细胞，骨髓穿刺常出现干抽，脾常明显肿大，并具有不同程度的骨质硬化。
CTI与百特国际（Baxter International）于2013年11月达成全球授权，合作开发和商业化pacritinib，CTI和百特将在美国联合商业化pacritinib，而百特拥有该药在美国以外地区所有适应症的独家商业化权利。
英文原文：FDA Grants Fast Track Designation to CTI BioPharma's Pacritinib, a Novel JAK2 Inhibitor for the Treatment of Myelofibrosis
SEATTLE, Aug. 7, 2014 --CTI BioPharma Corp. (CTI or the Company) (NASDAQ and MTA: CTIC) announced today that pacritinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease related thrombocytopenia, patients experiencing treatment emergent thrombocytopenia on other JAK2 therapy or patients who are intolerant to or whose symptoms are sub-optimally managed on other JAK2 therapy. Pacritinib is an oral tyrosine kinase inhibitor with dual activity against JAK2 and FLT3. The drug candidate is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis.
"We are very pleased that the pacritinib development program in myelofibrosis has been granted Fast Track designation, and we look forward to continuing to work closely with the FDA on this important drug candidate," stated James A. Bianco, M.D., President and CEO. "We believe that pacritinib's unique profile has the potential to serve an unmet medical need that currently exists in this patient population, particularly for those patients with disease or therapy-related low platelet counts."
The Fast Track process is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. An unmet need is a condition whose treatment or diagnosis is not addressed adequately by available therapy. The purpose of the Fast Track designation is to make important new drugs available to the patient earlier. The Fast Track program also enables a company to submit sections of the NDA on a rolling basis as data becomes available. This enables the FDA to review sections of the NDA as they are received, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the company has submitted the entire application to the FDA. A drug program with Fast Track designation enables the company to have early and frequent communication with the FDA in the development and review of the product candidate, often leading to faster drug approval and access by patients.
about the PERSIST Phase 3 Development Program of Pacritinib
based on pacritinib's efficacy and tolerability profile demonstrated to date, CTI is pursuing a broad approach to advancing this therapy for patients with myelofibrosis by conducting two Phase 3 clinical trials: one in a broad set of patients without limitations on blood platelet counts, the PERSIST-1 trial, and the other in patients with low platelet counts, the PERSIST-2 trial.
PERSIST-1:
In July 2014, CTI completed enrollment in the PERSIST-1 trial that was designed to enroll approximately 320 patients and is a randomized, open-label, multicenter trial comparing the efficacy and safety of pacritinib with that of best available therapy, other than JAK inhibitors, in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, without exclusion for low platelet counts. The primary endpoint is the percentage of patients achieving a greater than or equal to 35 percent reduction in spleen volume measured by MRI or CT from baseline to 24 weeks of treatment.
PERSIST-2:
In March 2014, CTI announced the initiation of the PERSIST-2 trial, which will evaluate pacritinib compared to best available therapy, including approved JAK2 inhibitors that are dosed according to product label, in patients with myelofibrosis whose platelet counts are less than or equal to 100,000/uL. The trial is designed to enroll up to 300 patients in North America, Europe, Australia and New Zealand. In October 2013, CTI reached agreement with the FDA on a Special Protocol Assessment (SPA) for the PERSIST-2 trial, which is a written agreement between CTI and the FDA regarding the planned design, endpoints and statistical analysis approach of the trial to be used in support of a potential NDA submission. Under the SPA, the agreed upon co-primary endpoints are the percentage of patients achieving a 35 percent or greater reduction in spleen volume measured by MRI or CT scan from baseline to 24 weeks of treatment and the percentage of patients achieving a Total Symptom Score (TSS) reduction of 50 percent or greater using six key symptoms as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to 24 weeks.
More details on the PERSIST-1 and PERSIST-2 trials can be found at www.clinicaltrials.gov.
about Pacritinib
Pacritinib is an oral tyrosine kinase inhibitor with dual activity against JAK2 and FLT3. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors.
In November 2013, CTI and Baxter International (Baxter) entered into a worldwide license agreement to develop and commercialize pacritinib in which CTI and Baxter will jointly commercialize pacritinib in the U.S. and Baxter has exclusive commercialization rights for all indications outside the U.S.
about Myelofibrosis
Myelofibrosis is classified as a myeloproliferative neoplasm and is a chronic bone marrow disorder. Myelofibrosis is caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response, scarring the bone marrow and limiting its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue and pain.
about CTI BioPharma
CTI BioPharma Corp. (NASDAQ and MTA: CTIC) is a biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies covering a spectrum of blood-related cancers that offer a unique benefit to patients and healthcare providers. CTI has a commercial presence in Europe and a late-stage development pipeline, including pacritinib, CTI's lead product candidate that is currently being studied in a Phase 3 program for the treatment of patients with myelofibrosis. CTI is headquartered in Seattle, Washington, with offices in London and Milan under the name CTI Life Sciences Limited.
抗体偶联药物涅槃重生
抗体偶联药物（antibody-drug conjugate，ADC）的研究可追溯到1980年代，但直到2000年，首个抗体偶联药物gemtuzumab ozogamicin（商品名Mylotarg，由辉瑞研发）才被FDA批准用于治疗急性粒细胞白血病。但由于偶联技术、靶向性、有效性等受限，完整的抗体偶联药物在血液里不稳定，导致致死性毒性的产生，该药于2010年撤市。这使得本就不明朗的ADC药物研发蒙上了一层阴影。
首个针对实体瘤ADC药物
ADC是将抗体与细胞毒性药物连接起来，通过抗体的靶向作用将细胞毒性药物靶向肿瘤，进而降低化疗中常见的药物非特异性的全身毒性。
随着武田/Seattle Genetics公司通过对原有技术的改进，利用自己的新型抗体偶联技术开发了brentuximab vedotin（SGN-35，商品名Adcetris）新型抗体偶联药物，并与2011年被FDA批准用于治疗霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤，2013年抗体偶联药物再次取得突破，基因泰克/ImmunoGen联合开发的Ado-trastuzumab emtansine（T-DM1，商品名Kadcyla）被FDA批准用于HER2阳性乳腺癌，这是首个针对实体瘤的抗体偶联药物。随着这两个药物的研发成功，ADC药物再次进入人们的研究视野。
设计多种偶联基团
目前走在开发最前列的ADC药物均使用传统的偶链技术（no-specific conjugation），最大的缺点就是得到的产品是一种每个抗体载有不同药物分子数的混合物；无法实现特定位置偶联药物，更重要的是临床评价难以得到均一数据。
针对这些缺点，定向偶联技术成为各大公司追逐的热点。使用定向偶联技术可使每个抗体上携带相同数目的药物分子数，得到均一性的ADC药物。利于药效学的研究和评估。并且在临床中可获得更加稳定的效果。
在中国市场开拓方面，Ambrx公司的Unatural Amino acid（pAcPhe）技术走在了前面，该公司在2013年6月同浙江医药签署《合作开发和许可协议》，进行新药的合作研发与商业化生产，进行应用于乳腺癌治疗的单克隆抗体药物аHer2-ADC的合作研发。
2014年4月底，Ambrx公司同浙江海正药业签署基于Unatural Amino acid（pAcPhe）技术的ADC药物进行开发和商业化合作协议。
抗体药物及疫苗是从单价药物向多价药物进行发展的。ADC也应该会走这个发展历程，即在同一个抗体链接几种相互协同的小分子来提高药物的药效。但是现在，在传统的偶链技术中，过度追求了在特定位点偶联特定分子数，忽略了偶联的多样性。
实用传统技术进行多价偶联药物，需要在一个抗体上同时偶联多种药物，这时抗体自身修饰链接基团的单一性，会造成混合型产品，无法保证每个抗体上同时携带不同的药物。
这个难题可以通过传统的偶链技术来解决，在进行传统偶链技术修饰时，可以设计多种不同的偶联基团，这就可以使用一种基团来针对带有对应基团的偶联子进行药物偶联。最终通过偶联子多样化改造进行多种药物的链接，实现多价偶联ADC药物。
Sovaldi 在印度只卖900美元，敢信吗？
作者：郭超伟 来源：中国新药杂志 发布日期：2014年8月8日
尽管丙肝药物Sovaldi在美国84000美元（12周）的定价已经惹毛了一些政客和医保付费者，但Gilead依然坚守自己的定价原则毫不动摇，并称从长远来看，Sovaldi是可以为美国的医保体系节省大笔医疗支出的。赞誉与口水齐飞之下，Sovaldi在上半年实现57.5亿美元的销售收入，佐证了该药在丙肝患者中受欢迎的程度。
Gilead从一开始就在全球范围内按照一个国家的国民收入情况为Sovaldi实行分层定价策略，主要分为低收入国家、低中等收入国家和高收入国家3类。。同样是在发达国家，Sovaldi在药品价格管控相对严格的德国售价是$66000，在政府议价能力更强的英国只有$57000，而在全球丙肝发病率最高的埃及以及创新药市场环境相对恶劣的印度，你知道Sovaldi的定价是多少吗？900美元，是的，你没看错，99%的折扣。而且Gilead执行总裁Gregg Alton曾向印度时报透露：“如果Gilead能与印度本土仿制药企业达成为印度患者生产该药的合作协议，Sovaldi未来的售价还会比900美元更低”。
印度目前大约有1200万丙肝患者，当前人均治疗成本在6000美元左右，需要注射给药24~48周，且通常伴随严重不良反应。Sovaldi使用更方便，治愈率高，不良反应少。按照世界银行的数据，2009~2013年美国公民的年均收入为53143美元，而印度公民的年均收入仅1499美元。Gilead在美国和印度为Sovaldi制订了天差地别的价格，很有业界良心的对不对？
其实这也是各制药企业在印度这个特殊医药市场的无奈之举。印度拥有医疗保险的人较少，药品支出大多需要民众自己付费，对于药企推出的一些优质高价新药，只要是公民必需，印度政府通常会找到各种理由给予强制许可。如果药物在专利期内即被印度一票药企仿制，原研厂家面对的不仅是该新药在印度市场的销售收入损失，还包括产品在全球范围失控的风险。比如拜耳的抗癌药Nexavar（索拉非尼）在2012年被印度政府强制许可给Natco进行仿制，定价比原研药的4000欧元低97%以上，拜耳至今仍在法庭上与Natco纠缠，以阻止Natco将仿制药卖至印度以外的国家。很可怕的是，Natco已经向印度专利局提出申请，要求否决Sovaldi在印度的专利授权，并允许Natco为印度本国公民生产价格更低的仿制药物。
印度市场的特殊情况似乎不能平息美国人对Sovaldi差别定价的怒火，同样的情绪也在欧洲各国蔓延，尽管已经略低于在美国的定价，但还是有14个欧洲国家打算联合起来与Gilead进行谈判，期望谈出一个更低的价格。
Sovaldi在上市首年无疑将为Gilead带来百亿美元收入，这会帮助Gilead快速收回前期的巨额成本。由于丙肝治疗的突破性进展，Sovaldi之后还有AbbVie、默沙东、BMS等药企的数个疗效优异的丙肝药物组合在未来12个月内集中上市。可以预料的是，等到丙肝药物市场有序竞争开始的哪一天，Gilead肯定会在Sovaldi的定价上有所松动，在这之前，Sovaldi还是会为大家倾情演绎一段新药销售史上的神话。
Ref: http://www.fiercepharma.com/stor ... -us-cost/2014-08-07
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