2014-12-10国内、国际信息大拼盘

Bluebird新型罕见贫血症药物LentiGlobin BB305临床研究进展顺利

                               
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发布日期：2014-12-10  来源：新药汇

Bluebird新型罕见贫血症药物LentiGlobin BB305临床研究进展顺利。

                               
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Bluebird公司最近透露，公司开发的用于治疗一种罕见遗传性血液疾病--重型β-地中海贫血症--的药物LentiGlobin BB305临床研究进展顺利。

重型β-地中海贫血症是一种由于β-球蛋白基因缺陷，导致患者机体无法产生足够的血红蛋白而出现的疾病。这种疾病的临床症状包括严重贫血和脾增大等。

LentiGlobin BB305利用经过修饰的慢病毒向患者体内输送正常基因片段，通过重组，能够使患者正常表达该基因产物。在今年的美国血液学会年会上，公司报告了使用其疗法的四名患者的状况，数据显示，在接受治疗后长达三个月的时间内，这些患者的病情都得到了明显的改善。而随后，Bluebird公司又公布了关于LentiGlobin BB305的另一项临床前期研究，在这一研究中，使用了这种药物的两名患者体内产生的β-球蛋白水平明显提升，且药物的时效分别达到了5个月和3个月。同时这些患者中并未观察到有明显副作用。这一消息无疑激励了投资者的热情，促使公司股价大涨。

不同于其他的基因疗法，LentiGlobin BB305并未直接将基因插入到患者细胞内，而是通过先分离患者的一部分造血干细胞，将正常β-球蛋白替换到这些细胞中，从而达到治疗效果。这样一方面便于研究人员控制基因的输送，另一方面也能明显降低这一药物潜在的副作用。根据BlueBird公司估计，全世界每年会有4万名新生儿患有这种罕见病。

罕见病是指那些发病率极低的疾病。罕见疾病又称"孤儿病"，在中国没有明确的定义。不过根据世界卫生组织（WHO）的定义，罕见病为患病人数占总人口的0.65‰～1‰的疾病。世界各国根据自己国家的具体情况，对罕见病的认定标准存在一定的差异。例如，美国将罕见病定义为每年患病人数少于20万人（或发病人口比例小于1/1500）的疾病。正是因为罕见病的患病人数过少，因此在早先许多生物医药厂家并未对这一领域进行过多关注.不过,随着FDA颁布了一系列罕见病研发的优惠政策后，也吸引了许多生物医药公司投入其中。如今，几乎所有的国际生物医药巨头，都在这一市场中有着自己的产品.

详细英文报道：

Bluebird bio's experimental therapy for the genetic blood disorder beta-thalassemia major is working just as the biotech ($BLUE) planned, using a single dose to wean two more patients off of the chronic transfusions required to treat the disease.

The disorder results from a defective beta-globin gene that stops patients from producing the hemoglobin they need, often resulting in symptoms like severe anemia and an enlarged spleen. Bluebird's treatment, LentiGlobin BB305, uses a modified lentivirus to deliver a corrective copy of the gene through a one-time infusion, ideally getting beta-thalassemia major patients back to manufacturing beta-globin on their own.

And, so far, LentiGlobin BB305 is doing exactly that. In preliminary results presented at the annual the American Society of Hematology meeting, the first four patients treated with bluebird's therapy remain transfusion-free after at least three months follow up, affirming the treatment's promise as a functional cure for the disease. That adds two more transfusion-free patients to the two bluebird disclosed over the summer, news that sent its shares up more than 50% in June. Bluebird's latest updat boosted its stock price as much as 40% after hours on Monday.

The new data come from two ongoing studies of LentiGlobin BB305. In the latest, bluebird has dosed 5 patients with beta-thalassemia major, finding that the first two are producing increasing amounts of beta-globin and have been transfusion-free for 5 and 3 months, respectively. The remaining three subjects need more time before bluebird can draw any conclusions on efficacy, the company said.

In the second study, involving two beta-thalassemia major patients and one with severe sickle cell disease, the two previously discussed subjects are still churning out beta-globin and remain free of the need for transfusions for 12 and 9 months, respectively. As for the sickle cell patient, bluebird said it's still too early to make efficacy inferences.

LentiGlobin BB305 has so far been well tolerated across both studies, the company said, with no gene therapy-related serious adverse events observed.

Now bluebird, a 2012 Fierce 15 honoree, is working to complete enrollment in both studies next year, targeting 22 patients in total. As the data on LentiGlobin BB305 mature, the biotech plans to start working with experts, patient groups and authorities to map out a regulatory plan for the treatment, Chief Medical Officer Dr. David Davidson said.

LentiGlobin BB305 differs from many of the other gene therapies in development around the world, which involve inserting corrective genes directly into a patient. Instead, bluebird's method works by removing a patient's hematopoietic stem cells, equipping them with a functional beta-globin gene and then reinserting them through infusion.

about 40,000 children are born with beta-thalassemia around the world each year, according to bluebird.

礼来/Incyte关节炎药物baricitinib关键III期临床试验大获成功

                               
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发布日期：2014-12-10  来源：生物谷

礼来口服关节炎药物baricitinib在首个关键III期研究大获成功，预示着该药有望在拥挤不堪的市场中开辟一块天地。

                               
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礼来和合作伙伴Incyte近日公布了类风湿性关节炎（RA）药物baricitinib关键III期RA-BEACON研究的积极顶线数据。

该研究在527例既往经至少一种抗肿瘤坏死因子（TNF）制剂（包括重磅药物阿达木单抗Humira和依那西普Enbrel）治疗失败正服用稳定剂量常规疾病修饰抗风湿药物（cDMARD）的中度至重度类风湿性关节炎（RA）患者中开展。

研究中，除了接受cDMARDs背景疗法外，患者还接受每日一次baricitinib或安慰剂治疗。研究结果表明，治疗12周后，与安慰剂相比，baricitinib达到了改善ACR20反应的主要终点。安全性方面，baricitinib的副作用与安慰剂相似，常见的不良反应包括头痛，上呼吸道感染和鼻咽炎。RA-BEACON研究是baricitinib III期项目的首个关键研究。礼来将于2015年在科学会议上公布数个关键III期试验的数据。。

抗肿瘤坏死因子（TNF）疗法如修美乐Humira（阿达木单抗）、类克Remicade（英夫利西单抗）美罗华Rituxan/MabThera（利妥昔单抗）、恩利Enbrel（依那西普）是全球最畅销的药物，这4种均位列《2013年最畅销的25个药物》榜单。而RA-BEACON研究的成功，预示着baricitinib有望在本已拥挤不堪的市场中开辟一块天地。

目前，礼来和Incyte正在开展一项大型III期项目，包括在美国开展的4个研究和在中国开展的1个研究，涉及3000例类风湿性关节炎（RA）患者，评估baricitinib的疗效及安全性。礼来预计将于2015年底完成美国的4个III期研究，并根据结果向FDA提交baricitinib的上市申请。

与常规的注射型TNF阻断剂不同，礼来的baricitinib是一种口服JAK抑制剂，旨在阻断炎症信号和治疗免疫学疾病（包括类风湿性关节炎）的根本病因。辉瑞的口服JAK抑制剂Xeljan于2012年获批上市，业界曾对该药寄予厚望，但上市之后却并没有如预期的很快达到行业预期，导致JAK抑制剂的前景暗淡不少；近日，巨头强生宣布终止与安斯泰来近10亿美元的合作，该项合作中同样涉及一种JAK抑制剂ASP015K，这一变故也多少给JAK抑制剂的前景带来了一些动荡。

英文原文：Lilly and Incyte's oral arthritis drug aces its first Phase III test

A new rheumatoid arthritis pill from Eli Lilly ($LLY) and Incyte ($INCY) beat out placebo in a pivotal trial, the first late-stage success for a drug the companies hope can carve out a space in a crowded market.

In a Phase III trial on 527 RA patients who failed on TNF inhibitors like Enbrel and Humira, Lilly and Incyte's baricitinib met its main goal of significantly improving disease score compared to placebo. On the safety side, baricitinib's side effect profile was similar to placebo, the companies said, with common adverse events including headache, upper respiratory tract infection and nasopharyngitis. The partners are releasing only top-line results for now, planning to divulge full data at a scientific meeting next year.

The success allows Lilly and Incyte to check the first box in their 3,000-patient late-stage program, which includes four ongoing trials in the U.S. and one in China. The two expect to complete the first four studies by the end of 2015, mapping a path to regulators from there.

"People with rheumatoid arthritis who have had an inadequate response to TNF inhibitors are generally considered to be the least responsive to subsequent treatments," Lilly Senior Vice President David Ricks said in a statement. "These results give us further confidence in the potential for baricitinib to be a meaningful treatment option for those suffering from this debilitating condition."

And unlike the injected TNF blockers that have brought in billions for AbbVie ($ABBV) and Amgen ($AMGN), baricitinib is an oral JAK inhibitor designed to block inflammatory signaling and treat the underlying cause of immune diseases including RA, all without the need for needles.

Meanwhile, JAK inhibitors for inflammatory disease have lost some of their luster of late, as Pfizer's ($PFE) Xeljanz has failed to catch on as quickly as analysts expected when it won approval in 2012, and Johnson & Johnson ($JNJ) has walked away from a nearly $1 billion deal with Astellas covering a similar treatment called ASP015K.

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