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2015年2月13日讯 /生物谷BIOON/ –血液病巨头百特国际（Baxter International）近日在芬兰赫尔辛基举行的第八届欧洲血友病及相关疾病协会（EAHAD）年会上公布了基因疗法临床项目的最新进展，其中一项I/II期开放标签临床试验评估了B型血液病基因疗法BAX 335的安全性和最佳剂量水平。该研究在16例B型血液病成人患者中开展，调查了递增剂量BAX 335的安全性，以确定最佳单剂量，研究主要终点是单剂量BAX 335静脉给药的安全性，次要终点包括评估最佳剂量所取得的稳定治疗性血浆FIX活性及药代动力学和药物免疫反应。
截止2014年底，3个剂量组共有6例患者经过治疗后证实具有剂量相关的反应。迄今为止，尚无患者体内产生FIX抑制剂。在2个最高剂量组，FIX活性水平在2个患者中水平提升10%左右，这些患者也未经历出血事件。其中一例患者显示肝酶水平升高，提示出现免疫反应，根据临床协议该患者目前正接受口服皮质类固醇治疗。这些免疫反应，在相关基因治疗研究中已有报道。目前百特正在对研究中其他患者进行筛查以获得更多的临床信息。
B型血有病患者体内缺乏产生凝血因子IX的能力，目前使用血浆来源或重组因子IX进行治疗。BAX 335是一种基因疗法，旨在为患者肝脏提供一种机制，使其在单剂量BAX 335治疗后的一段时间内开始生成凝血因子IX。
百特于2014年4月收购Chatham Therapeutics公司后，获得了其在研基因治疗项目。Chatham的生物纳米粒子（BNP）是一种基于重组腺相关病毒（rAAV）的先进基因治疗技术，在早期研究中已显示出巨大的治疗利益。除了B型血液病，百特也在推进评估基因疗法用于A型血液病的治疗。（生物谷Bioon.com）
英文原文：Baxter Provides Progress Update on Gene Therapy Program, Including Phase I/II Clinical Trial of BAX 355, Investigational Gene Therapy for Hemophilia B
DEERFIELD, Ill., FEBRUARY 12, 2015 – Baxter International Inc. (NYSE:BAX) today provided an update on its gene therapy program, including progress on the Phase I/II open-label clinical trial assessing the safety and optimal dosing level of BAX 335, an investigational factor IX (FIX) gene therapy treatment for hemophilia B, during a sponsored symposium at the 8th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) in Helsinki, Finland.
The trial is assessing the safety of ascending doses of BAX 335 to determine the optimal single dose in up to 16 adult patients with hemophilia B at treatment centers in the United States. The primary endpoint is the safety of a single dose of BAX 335 administered intravenously. Secondary endpoints include evaluation of the optimal dose to achieve stable therapeutic plasma FIX activity, as well as pharmacokinetics and immune response to treatment.
As of the end of 2014, a total of six patients in three dosing cohorts have been treated in the trial with evidence of a dose-related response. No patients have developed FIX inhibitors to date. In the two highest dose cohorts, FIX activity levels around 10 percent or above have been observed in two patients, who also experienced no bleeding events. One of these patients showed elevated levels of liver enzymes indicative of an immune response, which is being treated with oral corticosteroids, per protocol. Immune responses have been reported in previous studies with gene therapy technology. Additional patients are being screened and more information on the trial is available at www.clinicaltrials.gov , by using Identifier #01687608.
“We continue to make steady progress in advancing our hemophilia B program with this technology and look forward to better understanding the applicability of this technology platform in hemophilia A patients as well,” said John Orloff, MD, vice president and global head of research and development at Baxter BioScience. “With the potential to redefine the treatment of hemophilia, this gene therapy technology is a central part of our R&D focus as we prepare to become an independent company this year,”
Patients with hemophilia B lack the ability to produce clotting factor IX and are treated with plasma-derived or recombinant factor IX today. BAX 335 is designed to provide a mechanism for the patient’s own liver to begin producing factor IX over an extended period following a single dose of the genetically engineered treatment.
In April 2014, Baxter announced the acquisition of Chatham Therapeutics, LLC, an affiliate of Asklepios BioPharmaceutical, Inc. (AskBio), and its developmental gene therapy programs. Chatham’s Biological Nano Particles (BNP), an advanced recombinant adeno-associated virus- (rAAV-) based gene therapy technology, has shown potential therapeutic benefit in early studies. In addition to the research in hemophilia B, Baxter is also advancing plans to evaluate the gene therapy technology in the treatment of hemophilia A.
About Hemophilia B
Hemophilia B is the second most common type of hemophilia (also known as Christmas disease) and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding. Approximately 26,000 people worldwide, including more than 4,000 in the U.S., have been diagnosed with hemophilia B. Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.
About Baxter in Hemophilia
Baxter has more than 60 years of scientific experience in supporting the treatment needs of patients with hemophilia and has introduced a number of therapeutic firsts. Baxter has the broadest portfolio of hemophilia treatments and is able to meet individualized patient therapeutic needs by providing a range of options at each treatment stage. The company’s work focuses on optimizing hemophilia care and improving the lives of people worldwide living with bleeding disorders.