骨髓移植 奇美醫院年底成軍投入

自由時報-2012年06月06日 〔自由時報記者孟慶慈／台南報導〕骨髓移植是血液性惡性疾病治療的最後希望，雲嘉南地區現僅成大醫院從事自體、異體骨髓移植治療，很多患者需到北部求醫，奇美醫院年底將成立完整的骨髓移植團隊，投入相關治療行列，目前正積極訓練團隊成員。奇美醫院血液腫瘤科醫師吳鴻昌表示，骨髓移植是治癒嚴重再生不良性貧血、血癌、淋巴癌、先天性免疫缺損等疾病的最後希望；奇美醫院今年光是血液腫瘤科就有四名需移植的病患。吳鴻昌表示，雖然骨髓移植後感染、排斥的風險都很高，但骨髓移植是治療血液性惡性疾病唯一的希望，不到最後關頭不會提出，因此更需要完整的醫療團隊來照顧患者，所幸目前醫學精進，患者的存活率已大為提高。吳鴻昌指出，骨髓的捐贈者或來自親屬，或是一般的捐贈者，早期取捐贈者的骨髓必須進開刀房，全身麻醉，在髖骨位置穿數十針抽取骨髓。如今醫學進步，捐髓者只需事先服用白血球生長激素，讓幹細胞進入靜脈，只要挨一針就能收集到一袋血液幹細胞，對捐髓者來說輕鬆許多。吳鴻昌表示，奇美醫院八年前曾經為數名病患做過骨髓移植，但因故中止，現今重新整軍啟動，相關醫師已到外院接受訓練，他自己已在台大受訓一年，接下來是護理師、藥師等訓練，預定年底骨髓移植團隊正式成立。

NeoStem: An Investment In Both Stem Cell And Immunotherapy

June 5, 2012Chemistfrog  |  about: NBS Modern medicine is a result of centuries of observations, theories, hypotheses and experimentation. Many of the dramatic changes in our medical history have been sudden and often accidental while others are a product of years of surmising and the subsequent trial and error. Mankind is in the process of making its most abrupt revolution in medicine yet by focusing on a most amazing approach. This approach goes well beyond the last few decades of small molecule and chemically-synthesized compounds that are often designed to merely fight symptoms or to fight the immediate disease itself and not the cause of the disease/ailment or even aid longer-term recovery or prevention of recurrence. The new era has two major approaches with each deserving its own spotlight. The new, novel and creative source of these two approaches with one focusing primarily on injury treatment and tissue regeneration while the other focuses on protecting the body from its own self destruction due to cancer has been under our noses the whole time. We marvel at our chemical synthesis processes, our logic and deduction to fight injury and disease and our medical devices we tout as being the result of our creative genius and modern technology. Meanwhile, the solution to both the fight against cancer and the fight against injury and other cellular damage has been with us the entire time in the form of our own human body.ImmunotherapyThe immunotherapy approach to fighting cancer has been evolving rapidly with Dendreon's Provenge leading the charge with the first cancer vaccine approved by the FDA. This approach and the subsequent therapies and trials following all utilize our immunity system by teaching it that cancer cancers are foreign and should be attacked, just as viruses and bacteria should be. This is a growing area and is beginning to prove itself to be both legitimate and significant in its applications and is ushering in an entirely new era in the fight against cancer instead of the traditional chemotherapy, radiotherapy and surgery, each with their own successes but each with its own drawbacks

.Stem Cell Therapy  As this approach gains more traction, modern medicine is also beginning to take more note of another novel tool at their disposal in our own human body, regenerative medicine and more specifically cell therapy. Like the immunotherapy approach to helping the body by teaching it what it should fight and destroy from within, cell therapy helps the body by moving the powerful stem cells located in some areas (largely bone marrow) and moving them to areas of need. The source of these cells may be from within (autologous) or from an outside source (allogeneic). These cells may be either directly transplanted from one area to another or may be altered in an intermediate step to coax the cells into differentiating into the proper type of cell needed at the point of insertion for regeneration and repair

.Investor Opportunity is Phenomenal  Both the immunotherapy companies and stem cell companies are beginning to garner much attention by investors and large pharmaceuticals. However, the stem cell companies appear to be the more undervalued of the two and a great value investment as the increasing attention due to trial successes will likely begin driving the stock prices in the sector higher despite the degrading overall markets. The demand for goods and services in many sectors of the economy may wane as consumers cut costs. Meanwhile, the demand for health care is a fixed cost and one that only continues to grow as the population increases and ages.There are many stem cell companies with potential to have successful trials and growth through their own clinicals and subsequent marketing or licensing of their approved therapies. As with much of the biotech sector, the risks are typically obvious with a great deal of loss for ill-conceived investments and much upside for the correct decisions. One relatively unknown company whose growth potential appears to be unrealized is actually one of the biggest players in the field, NeoStem (NBS), an adult stem cell company. NeoStem's Progenitor Cell Therapy (PCT) division was actually involved in the manufacturing of the now-famous Dendreon's (DNDN) Provenge (immunotherapy approach) during its clinicals. The company has a host of other deals with customers such as Johnson & Johnson (JNJ), Baxter (BAX) and many others. As a supplier for each of these customers, not only has the company benefited from the obvious revenue from each of these, but it has also grown its knowledge base by manufacturing over 30,000 cell products.The experience, knowledge and revenue generated by being a valued source of cellular products for these companies is giving NeoStem exposure to potential pharmaceutical partners/suitors as well as knowledge as it grows its own pipeline, most notably their Amorcyte division's ARM-001. NeoStem initiated enrollment in their PreSERVE phase II stem cell therapy of AMR-001 for myocardial infarction on January 25th of this year. An autologous bone marrow derived cell therapy enriched for CD+34 cells, AMR-001 is administered 5-11 days after stent placement. The purpose of the treatment is to aid the body's natural repair mechanism by supplying the CD+34 stem cells that will aid in generating new blood vessels that will supply much needed oxygen and nutrients to facilitate repair and survival of cardiomyocytes (cells that comprise cardiac muscle), thus preserving heart function. With over 800K myocardial infarction events in the U.S. annually, and 20% of those having so much damage to their heart muscle tissue that the remaining muscle cannot compensate for the lost functionality, the area of need and associated market is huge for AMR-001. The phase II trial is just getting underway, and anything is possible with the upcoming data. If the data is as impressive as the phase I appeared to be, the upside for this small biotech can be great. A poor response, although a definite negative for the company and its current lead product, doesn't offer as much downside as the value in the company is currently more in its manufacturing sector (PCT) than their own pipeline.NeoStem's undervalued price is rapidly garnering attention as the stock price has soared over 33% since an April 10th dip due to a recent stock offering. This offering and the grossly oversold state it still resides at offers investors a likely phenomenal entry point into one of the most exciting and dynamic companies in not only the stem cell sector, but also the entire biotech field. The company has many notable catalysts coming up in 2012 and 2013 with deals coming in the forms of manufacturing contracts in their PCT division, updates on enrollment and interim data in their Amorcyte division's AMR-001 and a likely sale of their 51% stake in their Chinese subsidiary, Suzhou Erye Pharmaceutical. Time will only tell if, when and how much the sale of Suzhou will provide in terms of added cash to the company's cash base. The potential sale of Suzhou, the $6 million offering in March and the company's growing manufacturing contracts are each contributing to the bottom line and will likely soon create an even more solid stem cell company still currently in development phase but yet generating revenue to benefit share holders with increased earnings and additional money for financing their own clinicals.The risk obviously, in so many biotechs is largely offset here as their own pipeline is actually not the biggest source of optimism and revenue. However, the company does need to streamline somewhat to start generating a solid profit. A Suzhou sale announcement would be a welcome event as the company needs to streamline more and focus more on its core cell therapy divisions as well as the obvious cash infusion (amount yet to be determined or even hinted at in PR's). Investors are expecting the company to sell its stake in the Chinese pharmacy and for the proceeds to create a significant cash position for the company to develop its cell therapies. If for some reason this sale did not occur it would be a blow to the company, as it needs to abandon that aspect of the business and focus on the PCT and clinical development of its products.The value for this biotech is not solely based on hope and "potential sales" of an approved product in the future like many or even most biotechs, but rather it is based also on current manufacturing contracts as well as an upcoming divestiture. In fact, the only sizeable risks that I can identify are the questions surrounding the sale of its stake in the generic pharmacy to provide cash and in terms of its manufacturing business the company must show that clients are willing to sign long-term contracts that provide continuous revenue even after approval. The risks with all biotechs are generally the same in the developmental phase. Since AMR-001 is a new class of treatments investors must always question how accepting regulators will be to new therapies. Yet with approvals in cell therapy already being seen and more biotechnology companies choosing to focus on cell therapies it appears NeoStem is perfectly positioned to capitalize on the growing interest in the space, assuming that the space continues to grow.The headlines for NeoStem, Inc. should be exciting and potentially profitable for investors in the upcoming weeks, months and even years with steady and sustained growth likely due to a growing sector growing more dependent on it. Any positive outcomes on their clinicals are simply "icing on the cake". Investors making a proper entry into this sector's "cake" may fare very well in the short, mid and long-term; with or without icing.Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

胰岛素注射剂市场萎靡 寻找口服胰岛素

发布时间：2012/6/6 15:34:00 来源：药品资讯网信息中心 6年前，诺和诺德首席执行官索文森(Lars Soerensen)启动了"寻找胰岛素药丸"的工作。 现年66岁的法国人杰基·沙林(JackieChaline)每天都需要注射胰岛素维持生命。16年前被诊断出患有糖尿病后，在过去7年中，沙林使用了大约9000支胰岛素注射剂。"如果服药方式从注射变为口服，我就能彻底解放了。"沙林说。

预计销售峰值 就患者的适应性而言，口服给药与注射给药存在巨大差异。全球最大的胰岛素生产商诺和诺德正试图让沙林，以及数百万像她一样的糖尿病患者的愿望成真。近年来，诺和诺德与其他制药公司竞相开发"重磅炸弹"级口服胰岛素。为此，该公司至少花费了20亿美元，旨在令药物能避开人体自身的防御机制，并补充血液中的胰岛素。 诺和诺德首席科学官麦德斯·汤西嘉·汤姆森(Mads Krogsgaard Thomsen)表示，5年前，研发口服胰岛素成功的赔率为100万∶1，"而现在，我们越来越近50∶50了。" 分析师表示，如果诺和诺德的口服胰岛素研发成功，预计销售峰值将达50亿～100亿美元，并将长期成为全球畅销药物。 诺和诺德表示，口服胰岛素药物的临床研究进展顺利。本月初，该公司开展了一项新的临床研究。目前，糖尿病患者必须注射胰岛素，以防止血糖在血液中堆积。一个成功的口服胰岛素必须足够"强大"，在消化道中抵挡得住胃酸的袭击，并顺利经过肠壁进入肝脏。 汤姆森认为，口服胰岛素要做到上述这些关键点相当困难，"诺和诺德要么努力完成，要么放弃。"

革命性改变 糖尿病是因为人体缺乏将血糖转化成为能量的胰岛素引起的。国际糖尿病联合会估计，全球大约有3.66亿人患有糖尿病，每7秒就有一人因糖尿病死亡。 汤姆森认为，口服胰岛素不能完全取代注射用胰岛素，因为口服胰岛素只能适用于人体仍可以产生一些胰岛素的患者。相反，注射用胰岛素能让糖尿病患者及早得到治疗，因为医生不会等到口服胰岛素上市后，再来开处方。 内分泌专家认为，如果口服胰岛素能研发成功，影响将是革命性的，会有更多糖尿病患者转用这种新剂型。 沙林患有最常见的2型糖尿病。当初她对使用胰岛素具有强烈的抵触情绪，因为她害怕注射。7年过去了，她有时仍感到注射胰岛素是一件痛苦的事情。当她外出就餐时，她会迅速躲进卫生间，以免让其他人看到她在扎针。她还不得不在她的手臂、腹部和大腿之间翻转，以寻找完好的皮肤部位扎针。沙林说，吃药会改变所有这一切。 到目前为止，诺和诺德的长效口服胰岛素已在大鼠、比格犬和超过100个受试者身上进行测试。2月2日，该公司发布2011年财务报告时表示，被称为NN1953的口服胰岛素已完成了首轮临床试验，其中参加临床试验的受试者只需服药一次。 临床试验在德国杜塞尔多夫附近的Profil新陈代谢研究所进行。早些时候，另一种药物NN1952由于在早期试验中遭遇失败而被抛弃。

"违背自然的力量" 早在6年前，诺和诺德首席执行官拉尔斯·索文森(Lars Soerensen)就启动"寻找口服胰岛素"的工作。 诺和诺德急需补充新产品以应对赛诺菲和礼来的竞Ｄ壳埃霉菊群騀DA对其长效胰岛素注射剂Degludec的上市审批。Degludec的竞争对手为赛诺菲的最畅销药物来得时(Lantus)。诺和诺德希望Degludec上市后，从来得时手中夺取更多的市场份额。由于糖尿病治疗药利拉鲁肽(Victoza)和血友病治疗药诺其(Novoseven)的销售额不及预期，致使诺和诺德2012年第一季度的盈利普遍低于分析师预期。 "当我们吞下胰岛素口服药后，药物首先经过胃和肠道，在那里，药物将受到酸和酶的攻击，然后转变为被称为氨基酸的更小颗粒后，穿过肠壁，最后到达血液，进入肝脏。"汤姆森在描述口服胰岛素药物的吸收、代谢过程时表示，肠壁的功能是确保有毒的物质不进入人体，而诺和诺德研发的药物则要"违背自然的力量(Mother Nature)"。 为应对挑战，诺和诺德召集公司的科学家和外部研究人员，研究胰岛素药物制备工艺。 诺和诺德新聘用的科学家包括纳沙尼·布帕力(Nazaneen Pourkavoos)。布帕力曾成功帮助默沙东研发西格列汀(Janumet XR)缓释片，该药联合了西他列汀(Januvia)和二甲双胍(Metformin)。今年2月，FDA批准西格列汀用于治疗2型糖尿病。 布帕力的工作就是寻找到一个配方，让口服胰岛素通过肠壁。他拿起一片药片笑着说："这是实实在在的东西，也是迷人的东西，你想一下注射剂的针头，再看看这片药片，这就可以解释为什么我们不辞劳苦也要开发口服胰岛素。"

提高生物利用度 使口服胰岛素顺利通过肠壁，仅是其中一项挑战。研究人员必须延长该药在血液中的药效，并提高被人体吸收的程度，即生物利用度；诺和诺德已成功寻找到提高药效的方法，并致力于提高药物的生物利用度。 最后，科学家们必须避免药物在复杂的胃肠道中被吸收，例如患有腹泻的患者，可能由于经过胃肠道的时间过短，使人体不能适当地吸收胰岛素。每日一次服用口服胰岛素就能给予患者足够的胰岛素，以防止危险的低血糖发生。 一些规模较小的糖尿病药物制造商，如宾夕法尼亚州的Diasome制药公司、耶路撒冷的Oramed制药和海峡群岛的Diabetology公司，都试图解决这个问题，但是有些公司放弃了。4月，印度的百康制药公司表示，正寻找合作伙伴以进一步研发口服胰岛素药物。 分析师表示，诺和诺德口服胰岛素上市后，将侵占现有的胰岛素注射剂市场份额，致使其他公司被迫研发口服胰岛素。诺和诺德将在明年底准备进行口服胰岛素的中期临床试验。

拜瑞妥(Xarelto) 未获扩大使用支持

发布时间：2012/6/6 15:34:00 来源：药品资讯网信息中心 据预测，到2015年，拜瑞妥将创造7.99亿美元的销售额。 日前，强生和拜耳开发的血液稀释剂拜瑞妥(Xarelto)未能获得美国FDA一个顾问小组的支持，以扩大使用范围，用于心脏疾病患者预防心脏病发作和中风。

数据缺失 FDA专家委员会以6：4的投票结果(其中1票弃权)提出建议，反对将拜瑞妥批准用于急性冠脉综合征(ACS)患者，这是因为1000名患者中途退出了临床试验，导致缺失相应的研究数据。顾问小组成员表示，数据缺失令人头痛，这对数据的可解释性和推论形成了挑战。 FDA预计将在6月29日决定是否批准扩大拜瑞妥的使用范围。 ACS每年导致120万人住院治疗。预计市场总规模超过10亿美元。一旦获批用来治疗ACS，拜瑞妥将与阿斯利康的Brilinta和礼来的Effient展开竞争。预计扩大拜瑞妥使用范围的时间有可能被推迟3~12个月。 在15526名患者参加的一项后期临床研究中，近1300人较早退出了研究，他们撤回了可分享其健康信息的知情同意书。虽然研究人员对其中177名患者进行跟踪，但审评专家表示，数据缺失令其难以判断试验结果是否出现了偏差。

开展第二项研究 强生拥有拜瑞妥在美国的销售权，而拜耳负责在欧洲市场销售该药。自从去年7月以来，拜瑞妥一直被用来预防接受膝关节和髋关节手术后的患者可能发生的血栓。去年11月，FDA批准该药预防心律不齐患者可能发生的中风。 5月21日，FDA一名评审员在研究报告中建议批准将拜瑞妥用来治疗ACS。 该名评审员在报告中说，虽然拜瑞妥会增加严重出血的危险性，但使用拜瑞妥之后的效益风险比似乎不错，这主要是因为降低了心血管疾病的死亡几率。 根据报告，与安慰剂相比，使用2.5毫克的拜瑞妥可将心脏病发作和中风的危险性降低15%，但与此同时，它会导致致命性出血的危险性增加2倍，导致严重出血、颅内出血、出血性脑中风和轻微出血的危险性增加3倍。 顾问小组成员、克利夫兰诊所心血管医学部主任StevenNissen表示，强生和拜耳应该对拜瑞妥开展第二项研究，详细收集研究数据。 强生则认为，鉴于这项试验长达3年，患者中途退出研究的比例并不让人感到意外。 FDA药品评价和研究中心负责临床科学的副主任RobertTemple在投票期间表示，数据缺失的情况一直存在，FDA正在敦促两家公司弄清楚患者为何退出试验，而不是仅仅将这些人标记为撤回知情同意书的患者。 据预测，到2015年，拜瑞妥将创造7.99亿美元的销售额。

從毒性測試到新藥開發

  大約兩年前，一些藥物公司開始嘗試性地涉入幹細胞領域。現在，制藥行業越來越多地用幹細胞來測試藥物毒性，以發現潛在的新療法。  比如Cellular Dynamics公司出售人類心肌細胞，生產腦細胞和血管上皮細胞，還將推出一系列人類肝臟細胞。心肌細胞來自誘導多能幹細胞（iPS細胞）。湯姆森說，"基本上所有的大型制藥公司"都買過一些。  此外還有總部在英國的醫療技術公司通用電氣醫療集團（GE Healthcare）。3年前，英國幹細胞生物學家斯蒂芬·明格辭去學術工作，帶領通用電氣醫療集團進入幹細胞領域。他們出售人類心臟細胞已經一年有餘，這些細胞來自胚胎幹細胞，他們很快也會賣肝臟細胞。  最關鍵的問題是，在許多藥物問題的案例中，只有那些藥得到了美國食品和藥物管理局（FDA）等機構的許可並進入市場後才能發現其中的問題。明格說："這些藥只是通過了各種動物實驗，然後通過了制藥工業的I期、Ⅱ期、Ⅲ期臨床階段，獲得了FDA許可。"  "在這方面，許多動物模型並不得力。小鼠實驗雖然效率很高，但在臨床實驗後期卻不能在人類身上重復。因此多年前人們就開始使用試管模型，以此來代表人類疾病，這是一個巨大的進步。"位於加利福尼亞舊金山的生物制藥公司iPierian戰略與合作開發高級主管亞當·羅森塔爾說。  明格及其研究小組曾對心臟細胞進行盲評實驗，以檢驗這些細胞對各種不知名的藥物化合物的反應，看它們是否具有毒性。明格說，當藥物被打開時，他們發現細胞對那些已知有毒的化合物立刻起了反應。  使用幹細胞測試能帶來明顯的健康利益，可以在藥物上市之前消除其危險的副作用，同時也能避免繼續投入開發成本，節約了數百萬資金。  除了測試藥物毒性，幹細胞還是一種開發新藥的重要工具。Cellular Dynamics和通用電氣醫療集團兩家公司銷售的幹細胞，都有這方面的功用。  iPierian公司並不向其他藥物公司出售其產品，而是用於內部開發。他們正在研究治療老年癡呆症等神經退行性疾病的藥物。該公司不久前曾宣佈，他們正在開發一種瞄準tau蛋白的單克隆抗體，這種蛋白在老年癡呆症中起重要作用，此外還有其他與神經退行性疾病有關的蛋白質。公司表示，這些決策都是建立在幹細胞研究的成果之上的。 

未來之路影響深遠  這一新生領域也有著許多未知數。iPierian共同創始人、哈佛幹細胞研究院轉化醫學部主任李·魯賓說，比如能夠將幹細胞用於研究某種特殊類型的疾病還存在很多爭議，尤其是那些非遺傳性的或晚髮型的紊亂，以及與多組織間相互作用有關的疾病等。  目前，魯賓在用幹細胞作為一種脊椎肌肉萎縮疾病的模型，這是一類早髮型遺傳紊亂。他指出，將幹細胞用於藥物開發，有望成為發現特效藥物的更好途徑，但只有真正經過證明的技術，才稱得上是更好的方法體系。  "目前，人類胚胎幹細胞和誘導多能幹細胞所做的，只是提供一種途徑，讓人們能利用人體最基本的物質材料進行基礎研究。"湯姆森指出，幹細胞還可能有更廣闊的用途，不止于藥物開發研究。有了這些細胞，我們能從更多細節層面理解人體。究竟要怎樣使用它們，還不能定論，但其必將對人類醫學產生深遠影響。（記者常麗君綜合外電）