市场观点:肝病大会看未来生技股

StephenW

Market opinion

Biotech stocks to watch ahead of liver disease conference

Hepatitis B

Companies to watch in hepatitis B include Arrowhead Research, whose shares took a massive tumble last month as data on the drug's efficacy disappointed investors.

"I would argue it's really too early to make a judgment call there, because we're clearly going to need to see some fairly long duration treatment regimens at this point to see what's truly going to happen to the hepatitis B virus," Baird's Skorney said.

Arrowhead is likely to present some more detailed data, though key questions from investors center around timelines for testing higher doses of the drug, Deutsche Bank's Young said.

Investors are also likely to be curious about private company Replicor, which has "shown some hepatitis B data that I can only characterize as really fantastic," Skorney said. "Most investors are scratching their heads if it can even be real," he said, noting the company has only a handful of employees and very little capital, and ran its study in a developing country.

Though development of new drugs across hepatitis B is early, the opportunity is large—it's the most common cause of liver disease. 5,000 patients die each year in the U.S. from liver failure, according to Cowen, and cure rates are very low. Skorney said cure rates are 10 percent or less, compared with more than 90 percent with new regimens in hepatitis C.

市场观点

生技股看未来肝病大会

B型肝炎

公司在乙肝收看包括箭头的研究，其股份采取了大规模的暴跌上个月因为对药物的疗效数据令投资者失望。

“我认为这真的太早做出判断调用那里，因为我们显然将需要看到一些相当长时间的治疗方案，在这一点上，看看有什么是真正将要发生的乙肝病毒，”Baird的Skorney说。

箭头很可能会提出一些更详细的数据，但投资者的关键问题围绕时限测试更高剂量的药物，德意志银行的Young说。

投资者也可能会好奇私营公司Replicor，这“显示出一些乙肝的数据，我只能形容为真太棒了，”Skorney说。 “大多数投资者摸不着头脑，如果它甚至可以是真实的，”他说，并指出该公司只有少数员工和很少的资金，跑它在发展中国家的研究。

虽然在整个乙型肝炎发展的新药物是早，机会是大是肝脏疾病的最常见原因。 5000名患者，每年死于肝功能衰竭在美国，据考恩和治愈率很低。 Skorney所述的治愈率为10％或更小，具有90％以上，在丙型肝炎的新的治疗方案相比

hao2014

投资者也可能会好奇私营公司Replicor，这“显示出一些乙肝的数据，我只能形容为真太棒了，”Skorney说。 “大多数投资者摸不着头脑，如果它甚至可以是真实的，”他说，并指出该公司只有少数员工和很少的资金，跑它在发展中国家的研究。

一点不错
画饼充饥好几年了
还在不紧不慢试验

咬牙硬挺

连箭头公司也要失败了？

重韧

箭头的数据在双11当天应该有了。

一字

我坚信乙友们离战胜的目标已经越来越近。

StephenW

After hepatitis C cure, companies target next big liver disease market                                                              Sunday, November 09, 2014 8:07 a.m. EST                                                                                         
                                                                                                                                                                 By Bill Berkrot
NEW YORK (Reuters) - Now that new medicines promise to cure millions of hepatitis C patients in coming years, drugmakers including Gilead Sciences Inc are turning their attention to other liver diseases, with a potential market that could rival the success of statins, which generated more than $30 billion a year in sales at their peak.
Several companies are working on treatments for hepatitis B, which can be controlled but not yet cured, and for fatty liver conditions caused by rising obesity, which without treatment could affect half of all Americans by 2030, according to the American Liver Foundation (ALF). Some of the drugs will address advanced fibrosis and cirrhosis, which are the scarring that virtually all liver diseases cause without effective treatments. Each of these drugs, once approved, could reach annual sales of as much as $10 billion, industry analysts said.
    Most of the treatments are now in early Phase I or Phase II clinical trials, with more informative interim data on several expected over the course of the next year.
Gilead, which was first to market with its hepatitis C cure Sovaldi late last year and has been racking up about $3 billion in sales each quarter, is a solid bet to be among the leaders in the next wave of liver therapies, experts said.
"The Gilead program is encouraging," said Dr. Naga Chalasani, director of gastroenterology and hepatology at Indiana University Hospital in Indianapolis, who is participating in clinical trials of promising drugs from Gilead and others.
Drugmakers are working to address the fatty liver disease known as NASH, or nonalcoholic steatohepatitis. Without treatment, NASH can progress to liver-destroying cirrhosis and potentially cancer.
ALF estimates that non-alcoholic fatty liver disease, including NASH, affects up to 30 percent of people in the United States. It can be caused by bad diets and alcohol abuse, and has also been tied to diabetes.
"We have no treatment for that condition other than tell a patient they need to lose weight," said Dr. Mauricio Lisker-Melman, director of the hepatology program at Washington University School of Medicine in St Louis.
    Intercept Pharmaceuticals has attracted the most attention. Just released final data from a mid-stage clinical trial showed its obeticholic acid halted NASH progression and improved liver scarring in primarily moderately ill patients. "For now, no one else has demonstrated an antifibrotic effect in this population, and I believe we are ahead of the pack in that sense," said Intercept Chief Executive Mark Pruzanski.
Intercept plans to begin a Phase III trial with at least 1,000 more seriously ill patients next year.
Dr. Scott Friedman, dean for therapeutic discovery at Mt. Sinai Hospital in New York, who has worked with virtually all the companies in the field, said most were first testing drugs in patients whose liver damage is not advanced.
"Gilead has sort of leapfrogged that," Friedman said, tackling more serious damage, as its simtuzumab targets fibrotic scarring directly, rather than inflammation or other drivers of disease. Reversing cirrhosis and improving liver function is "the highest bar I can think of in this business, and it would be spectacular," he said.
    Gilead faces competition from several smaller companies with promising drugs in development, including Intercept, France's Genfit, Israel's Galmed, Galectin Therapeutics, Conatus Pharmaceuticals and Raptor Pharmaceuticals, specialists said.
    Gilead's antibody simtuzumab blocks an enzyme called LOXL2 that is directly involved in laying down bands of collagen that form the scar tissue behind cirrhosis. The collagen bands, which result from a wide variety of assaults on the liver, including alcohol and drug abuse, cross link haphazardly to destroy the liver's architecture and function.
Gilead expects to have a strong indication of whether its drug is working when one-year data from a two-year Phase II study becomes available next year.
"We have a very active research program," said Mani Subramanian, head of liver disease clinical research at Gilead. "We're targeting everything: metabolic issues, inflammation and fibrosis directly." He acknowledged challenges faced by drugmakers trying to address more advanced liver disease: "It's been a graveyard for drugs that try to reverse fibrosis," Subramanian said.
    NOT FOR FAINT OF HEART
    Chalasani at Indiana University Hospital estimated there may be 20 different drugs being tried by various drug companies that seem to be good targets.
But betting on them is not for the faint of heart. Intercept's shares shot from about $72 to over $400 in a matter of days in January after it was announced the trial of its drug would meet the intended goal. On the flip side, Galectin lost nearly two thirds of its value in July, when its NASH drug using a different approach had a setback in a Phase I trial.
    Conatus is first testing its drug, emricasan, in patients facing acute liver failure, which has a 50 percent mortality rate in 28 days. Chief Executive Steven Mento said the goal was to "rescue these patients and prevent catastrophic organ failure." The company plans to work its way back, testing on less severely ill patients. The drug targets inflammation and excessive cell death seen as drivers of the disease.
    Dr. David Bernstein, chief of hepatology at North Shore University Hospital in Manhasset, N.Y., called the Conatus drug exciting and the initial trial a sensible approach.
    "There's limited downside because there's nothing else that can be done anyway," said Bernstein, who expects to be involved in future emricasan trials. "If you can reverse cirrhosis, you really will change the impact of liver disease worldwide."
Drugs that succeed in reversing cirrhosis "can be as big a class as the class of statins," said Conatus's Mento, referring to cholesterol drugs, such as Pfizer's Lipitor, which alone at its peak had annual sales of about $13 billion.
    Raptor, by contrast, is developing a drug for NASH in children, a growing problem that has left liver specialists fearing an obese generation that could require liver transplants in the prime of life.
    Raptor is testing a drug already approved for use in children for an extremely rare kidney disease. "In terms of safety, it's well established," said Raptor President and CEO designate Julie Anne Smith. It is now engaged in a year-long mid-stage trial of 169 children whose NASH was confirmed by liver biopsy with data expected in the first half of next year.
    Companies are waiting for the U.S. Food and Drug Administration to outline what it will take to approve a NASH drug. "The FDA is struggling with what constitutes a meaningful improvement with a patient," Gilead's Subramanian said.
Goals such as reducing fat buildup or modestly improving fibrosis would likely be simpler and quicker to achieve, for example, than avoiding need for liver transplants.
    The FDA is working "to identify clinically meaningful endpoints for NASH and related liver diseases to help guide drug development," it said in a statement.
The uncertainty from the FDA also creates risks for investors and has led some analysts to focus on other liver therapies. RBC Capital Markets analyst Michael Yee favors companies taking on hepatitis B, such as Arrowhead Research Corp, Canada's Tekmira Pharmaceuticals, Gilead and Isis Pharmaceuticals in partnership with GlaxoSmithKline. And one private company not to be ignored, OnCore Biopharma, founded by former Pharmasset executives, including the inventor of Gilead's Sovaldi.
    While finding a cure for hepatitis B will not be easy, trials would mirror those for hepatitis C, with a simple blood test yielding clear results in months rather than years.
(Reporting by Bill Berkrot. Editing by Michele Gershberg and John Pickering)

后丙型肝炎治愈，公司瞄准的下一个大肝病市场
周日，2014年11月9日上午08点07分美国东部时间

比尔Berkrot

纽约（路透社） - 现在，新的药品保证治愈数以百万计的丙型肝炎患者在未来几年内，包括制药公司吉利德科学公司正在把注意力转移到其他肝脏疾病，有可能他汀类药物相媲美的成功，它产生的潜在市场更多的是每年30美元十亿的销售额在其鼎盛时期。

有几家公司正在为乙型肝炎，其可以控制，但尚未固化的，而对于由肥胖引起的上升，其未经治疗可能影响一半的美国人在2030年脂肪肝的治疗条件，根据美国肝脏基金会（ALF） 。有些药物会针对晚期肝纤维化和肝硬化，这是疤痕，几乎所有的肝脏疾病导致没有有效的治疗方法。这些药物，一旦获批，可达到年销售额为10美元之多十亿，业内人士分析说。

   大部分的治疗是目前早期阶段I或II期临床试验，预计在未来一年中的几个更多的信息临时数据。

Gilead公司，这是第一个向市场推出了它的丙型肝炎治疗Sovaldi去年年底，并已费尽了约30十亿的销售额每个季度，是一种固态的赌注是在肝的治疗下一波的领导人，专家说。

“基列的计划是令人鼓舞的，”娜迦Chalasani医生，胃肠病学和肝病学在印第安纳大学医院在印第安纳波利斯主任，谁是参与前景的药物从基列和其他临床试验中说。

制药公司正在努力解决脂肪肝称为NASH，或者非酒精性脂肪性肝炎。如果不进行治疗，NASH可进展为肝，肝硬化破坏和潜在的癌症。

ALF的估计，非酒精性脂肪肝疾病，包括NASH的，会影响到的人在美国30％以上。它可以由不良饮食和酒精滥用引起的，并且也被连接到糖尿病。

“我们没有任何治疗的情况不是告诉他们需要减肥的病人等，”博士毛Lisker - 梅尔曼，在华盛顿大学医学院圣路易斯的肝病项目的主任。

   拦截制药吸引了最多的关注。只是从一个中间级的临床试验公布最后的数据显示，其obeticholic酸暂停NASH的进展和改善肝瘢痕形成中主要是适度病患者。 “现在，没有人表现出在这一人群中的抗纤维化作用，我相信我们未来在这个意义上的包，”拦截首席执行官Mark Pruzanski说。

拦截计划开始一项III期临床试验至少有1000多个重病患者在明年。

斯科特·弗里德曼博士，院长的治疗发现，在山西奈山医院在纽约，谁曾与几乎所有的公司在该领域的工作，说，大多数人第一个测试药物在患者的肝脏损害并不先进。

“之类的吉利德已经一举超越了，”弗里德曼说，直接打击更严重的伤害，因为它的simtuzumab目标纤维化瘢痕形成，而不是炎症或其他疾病的司机。逆转肝硬化，改善肝功能是“最高的吧，我能想到的在这个行业，这将是壮观的，”他说。

    Gilead公司面临着来自几个较小的公司有前景的药物开发，其中包括拦截，法国的Genfit，以色列Galmed，半乳糖凝集素治疗，自然倾向制药和猛禽制药的竞争，专家说。

    Gilead公司抗体simtuzumab块称为LOXL2的酶直接参与放下形成背后肝硬化疤痕组织胶原的频带。胶原蛋白条带，从对肝脏有各种各样的攻击，包括酗酒和滥用药物而导致，交联随意破坏肝脏的结构和功能。

Gilead公司预计将有是否当从一个为期两年的II期临床试验为期一年的数据可用，明年它的药物正在一个强烈的信号。

“我们有一个非常活跃的研究项目，”玛尼萨勃拉曼尼亚，肝脏疾病的临床研究，在基列的负责人说。 “我们瞄准的一切：代谢问题，炎症和纤维化直接。”他承认所面临的制药商设法解决更先进的肝脏疾病的挑战：“这是一个墓地的药物，试图逆转纤维化，”萨勃拉曼尼亚说。

    不适合心脏隐隐

    Chalasani在美国印第安纳大学医院，估计可能有20种不同的药物正在试图通过各种药物的公司，似乎是不错的目标。

但投注他们是不是心脏虚弱。大约72美元拦截的股票出手超过$400天的问题在一月份曾宣布其药物会达到预期目标的审判后。在另一面，半乳糖凝集素在7月份的时候使用不同的方法其NASH的药物已经在I期临床试验受挫下跌了近三分之二的价值。

    自然倾向是第一测试其药物，emricasan，在面对急性肝功能衰竭，其中有一个死亡率在28天中的50％的患者。行政总裁史蒂芬Mento表示，目标是“拯救这些病人，防止灾难性脏器功能衰竭。”该公司计划将其方式工作回来，检测就少病情严重的病人。的药物靶标炎症和过度的细胞死亡被视为该疾病的驱动程序。

    大卫·伯恩斯坦博士，肝脏病学首席北岸大学医院的Manhasset，NY，称为自然倾向的药物刺激，初审明智的做法。

    “有下跌空间有限，因为没有什么别的可无论如何做，”伯恩斯坦，谁希望能够参与未来emricasan试验说道。 “如果你能逆转肝硬化，你真的会改变肝脏疾病的影响，世界各地的。”

那些成功逆转肝硬化的药物“可以作为一个大的类作为他汀类的，说：”自然倾向的Mento，指的是胆固醇的药物，如辉瑞公司的立普妥，因为只有在其高峰期年销售额约为130十亿。

    猛禽，相反，正在开发一种药物，纳什在孩子，一个日益严重的问题已左半肝专家担心肥胖的产生，可能需要在壮年肝脏移植手术。

    猛禽正在测试已批准用于儿童的一种极为罕见的肾脏疾病的药物。 “在安全性方面，它的确立，说：”猛禽总裁兼首席执行官朱莉指定安妮·史密斯。它现在从事的169名儿童，其NASH证实了肝活检预计在明年上半年的数据长达一年的中期阶段试验。

    公司正在等待美国食品和药物管理局，阐述将采取什么批准纳什的药物。 “FDA正在挣扎着什么构成与病人有意义的改进，”基列的萨勃拉曼尼亚说。

目标，例如减少脂肪积累或小幅改善纤维化可能会是更简单和更快地实现，例如，比避免需要肝脏移植。

    FDA正“，以确定纳什和相关的肝脏疾病临床意义的终点，以帮助指导药物开发，”它在一份声明中说。

从FDA的不确定性也对投资者造成的风险，并导致一些分析师把重点放在其他肝病的治疗。 RBC Capital Markets的分析师Michael议有利于公司以乙肝，如箭头研究公司，加拿大Tekmira制药，基列和Isis制药公司结成合作伙伴葛兰素史克公司。和一个私营公司不可忽视的，OnCore生物制药，由前Pharmasset高管，包括Gilead公司Sovaldi的发明者创立。

    虽然寻找治疗乙肝并不容易，试验将反映这些丙型肝炎，有一个简单的血液测试，得到清晰的结果在几个月而不是几年。

（由比尔Berkrot。编辑报告由Michele Gershberg和约翰·皮克林）