Simtuzumab，抗肝纤维化的单克隆抗体的赖氨酰氧化酶像2（LOXL2

StephenW

Simtuzumab, an Antifibrotic Monoclonal Antibody Against Lysyl Oxidase-Like 2 (LOXL2) Enzyme, Is Safe and Well Tolerated in Patients With Liver Disease - (05/30/13)
http://www.natap.org/2013/EASL/EASL_115.htm
Pilot Study of GS-6624 in the Treatment of Liver Fibrosis
This study will evaluate the safety and tolerability of GS-6624 in patients with fibrosis of the liver.

Pilot Study of GS-6624 in the Treatment of Liver Fibrosis
http://www.clinicaltrials.gov/ct2/show/NCT01452308?term=Simtuzumab&rank=3

        Fatty liver disease, the accumulation of fat in liver cells, is the number one liver disease in the United States and a silent killer of epidemic proportion. The accumulated fat leads to inflammation that eventually leads to fibrosis, or scarring of the liver. In turn, the fibrosis leads to cirrhosis of the liver, an irreversible disease largely only resolved through transplantation. There is also an association between advanced fatty liver disease with fibrosis and liver cancer.

The problems with hoping for a liver transplant are that only about 6,300 liver transplants happen in the U.S. each year, it is a major procedure requiring lifelong immune suppression, and those that receive a transplant have a risk of fatty liver disease reoccurring.

Even more problematic, fatty liver disease is essentially asymptomatic until the latter stages. The disease is usually only diagnosed via routine screening for elevated enzymes, a seasoned physician requesting subsequent imaging tests and then a liver biopsy to confirm. To that end, fatty liver disease is often times not diagnosed until it has reached more advanced stages, a time when nothing can be done to reverse the damage.

For most, hearing "cirrhosis" brings to mind images of alcohol abuse. While that is certainly a pathway, fatty liver disease is closely associated with obesity and diabetes, two diseases spiraling out of control in the U.S. and other countries. Further, nonalcoholic fatty liver disease (NAFLD) is affecting about 30 percent of the U.S. population, without any FDA-approved treatment options.

        Gilead has their hand in the business with simtuzumab, a monoclonal antibody, in mid-stage clinical trials for liver fibrosis resulting from Nonalcoholic Steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease.

Raptor Pharmaceutical Corp. is developing RP103 as a treatment for NASH in children. NASH is the most common serious complication of childhood obesity. In June 2012, the first patient of an expected 160 patients was dosed with RP103 in a Phase IIb trial. The pediatric participants are to receive 52 weeks of RP103 treatment. Previously, a small-scale Phase IIa trial provided promising results with 7 of 11 patients achieving a greater than 50-percent reduction in alanine transaminase (ALT) and aspartate transaminase (AST) levels, two enzymes that are measured as standards in fatty liver disease care.                                          
Galectin Therapeutics Inc. is focusing its carbohydrate technology to develop drug candidates for fibrotic disease and cancer. Earlier this month, the company submitted a Fast Track application to the FDA, looking to expedite its GR-MD-02 for treatment of NASH in patients with advanced fibrosis. GR-MD-02 targets inhibiting galectin-3, a key protein in the pathogenesis of NASH and fibrosis. Outside of fibrosis and cancer, galectin-3 is also known to play a substantial role in the progression of heart disease.
http://www.galectintherapeutics.com/technology/fibrosis.php

        Galectin is in the midst of enrolling for a Phase I trial in NASH/advanced fibrosis patients. The trial will aim to expand upon and replicate the robust treatment effects of GR-MD-02 in laboratory studies that showed the therapy to not only be able to reduce inflammation, but also reverse established fibrosis and cirrhosis in animal models. The trial is being conducted at six clinical sites in the U.S. and comprised of approximately 32 patients.

While termed a Phase I trial, the patient population and the configuration of the protocol has more of the feel of a Phase Ib. The trial will be comprised of patients with NASH with stage 3 fibrosis and will evaluate four weekly doses of GR-MD-02. The main goal of an initial trial is to evaluate safety, but the multiple doses in late-stage patients and the monitoring of a variety of biomarkers will possibly open the door for efficacy to be demonstrated, obviously a pleasant secondary endpoint that could act as a significant stock price catalyst if shown.

Galectin is employing a unique strategy to focus on late-stage conditions of fatty liver disease that differentiates the company from Raptor and others that are targeting earlier stages (the onset of fat accumulation and inflammation) of fibrosis and NASH…. It can take a decade or more for NASH to develop into fibrosis and cirrhosis. Simply, the etiology of NASH makes it very difficult to determine which NASH patients will develop fibrosis or cirrhosis, presenting it's own set of challenges in trying to address the disease at early stages without attention to curative effects for scarred liver tissue.                                          

StephenW

Simtuzumab，抗肝纤维化的单克隆抗体的赖氨酰氧化酶像2（LOXL2）酶，是安全和良好的耐受性肝病患者 - （13年5月30日）

GS-6624在治疗肝纤维化的初步研究
这项研究将评估GS-6624的安全性和耐受性肝纤维化患者。

GS-6624在治疗肝纤维化的初步研究


        脂肪肝，肝细胞内脂肪的积聚，是在美国的头号肝病疫情比例和一种无声的杀手。累积脂肪过多会导致炎症，最终导致纤维化，肝脏上的疤痕。反过来，纤维化导致肝硬化，一种不可逆的疾病在很大程度上只能通过移植解决。还有先进的脂肪性肝病与肝纤维化和肝癌之间的关联。

希望能为肝脏移植的问题是发生在美国，每年只有约6300例肝脏移植手术，这是一个重要的过程，需要终身免疫抑制，那些接受移植手术的风险有脂肪肝疾病的再次发生。

更成问题，本质上是无症状脂肪肝疾病，直到后者的阶段。本病通常只酶升高，经验丰富的医师，要求后续的影像学检查肝活检以明确诊断，通过常规筛查。为此，脂肪肝等疾病往往是不能确诊的时间，直到它已达到了更先进的阶段，没有什么可以做的时候，以扭转损害。

对于大多数人来说听到“肝硬化”，使我想起酗酒的图像。虽然这无疑是一个途径，脂肪肝等疾病密切相关，肥胖和糖尿病，这两种疾病在美国和其他国家的控制失控。此外，非酒精性脂肪性肝病（NAFLD）是影响​​美国总人口的30％左右，没有任何FDA批准的治疗选择。

        Gilead公司都有自己的手在商业与simtuzumab，单克隆抗体，导致肝纤维化非酒精性脂肪性肝炎（NASH），非酒精性脂肪肝疾病的一种高级形式，在中期阶段的临床试验。

猛禽制药公司正在开发一种治疗NASH的儿童RP103。纳什儿童肥胖是最常见的严重并发症。 2012年6月，第一剂量RP103预期的160例患者的IIb期试验。的儿科参与者接受52周的RP103治疗。在此之前，一个小规模的IIa期临床试验的11例患者中有7例实现了大于50％的降低谷丙转氨酶（ALT）和谷草转氨酶（AST）的水平，这两种酶在脂肪肝疾病的标准计量提供了可喜的成果，照顾。
半乳糖凝集素Therapeutics公司的重点是其碳水化合物技术开发的候选药物纤维化疾病和癌症。本月早些时候，该公司向FDA提交了快车道申请，寻找NASH的治疗晚期肝纤维化患者，以加快其GR-MD-02。 GR-MD-02的目标抑制半乳糖凝集素-3，NASH和纤维化的发病机制中的关键蛋白。纤维化和癌症之外，也被称为半乳糖凝集素-3心脏疾病的进展中发挥重要作用。
http://www.galectintherapeutics.com/technology/fibrosis.php

        半乳糖凝集素是在一片招收NASH /晚期肝纤维化患者的I期临床试验。该试验将致力于扩大后，在实验室研究表明该疗法不仅能够减少炎症复制GR-MD-02强大的治疗效果，但也扭转既定的纤维化和肝硬化的动物模型。在6个临床试验点在美国进行审判，包括约32名患者。

虽然被称为I期临床试验，患者人口和配置的协议有更多的Ib期的手感。该试验将包括第3阶段纤维化和NASH患者将评估四个每周剂量GR-MD-02。初始试验的主要目的是评估安全性，但在晚期患者中，多剂量监测多种生物标志物可能会开门疗效证明，显然是一个令人愉快的次要终点可以作为重要的股价催化剂所示。

半乳糖凝集素是采用一个独特的战略，把重点放在后期脂肪肝疾病的区分猛禽和其他针对早期阶段的公司（脂肪积累和炎症纤维化和NASH）发病....它可能需要十年或更长时间，纳什发展成肝纤维化和肝硬化。简单地说，NASH的病因很难确定NASH患者将发展为肝纤维化或肝硬化，呈现它自己的挑战，试图解决疾病的早期阶段，而不注重疗效伤痕累累的肝组织。

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