强生丙肝药物OLYSIO（simeprevir）获欧盟批准 发布日期：2014-06-01 来源：新药汇
OLYSIO的获批，是基于II期COSMOS、3个关键III期QUEST-1、QUEST-2、PROMISE的数据。丙型肝炎（HCV）是一种血源性传染性肝脏疾病，若不及时治疗，可能对肝脏造成重大损害。
关于OLYSIO（simeprevir）：
Simeprevir是新一代NS3/4A蛋白酶抑制剂，为每日一次的口服药物，由Medivir公司和杨森（Janssen）联合开发，用于治疗慢性丙型肝炎成年患者的代偿性肝病，包括各个阶段的肝纤维化，其工作原理是通过阻断蛋白酶，来抑制HCV在肝脏细胞中的复制。
simeprevir分别于2013年9月和11月获日本（在日本的商品名为Sovriad）和FDA批准，与聚乙二醇化干扰素和利巴韦林（ribavirin）联合用药，用于基因型-1慢性丙型肝炎病毒（HCV）感染者的治疗。
simeprevir是一种新的直接作用抗病毒药物，也是第二代蛋白酶抑制剂，给药方式为：simeprevir+聚乙二醇干扰素+利巴韦林联合治疗12周，随后进行聚乙二醇干扰素+利巴韦林治疗12周或36周。
OLYSIO™ (simeprevir) receives marketing authorisation in the European unio for the treatment of adults with hepatitis C genotype 1 and 4 infection
Simeprevir provides a new triple therapy treatment option, as well as the first ever 12-week interferon-free and ribavirin independent treatment regimen, in combination with sofosbuvir, for appropriate patients in Europe
BEERSE, BELGIUM [May 16, 2014] Janssen-Cilag International NV today announced that its next generation protease inhibitor (PI) OLYSIOTM (simeprevir) has been granted marketing authorisation by the European Commission (EC) for the treatment of adults with genotype 1 and 4 chronic hepatitis C (CHC), in combination with other medicinal products, which includes1:
This marketing authorisation represents a significant milestone in the development of new triple therapy hepatitis C (HCV) treatment options for genotype 1 and 4 patients. It also includes simeprevir as part of an all oral 12-week IFN-free direct-acting antiviral (DAA) regimen with or without RBV, in genotype 1 or 4 patients, who are intolerant to or ineligible for IFN treatment.[1]
“The EC marketing authorisation for simeprevir is a great milestone as it adds an important new treatment option for patients, demonstrating the continued role of triple therapy in the treatment of HCV. In addition, the introduction of an all oral, 12-week interferon-free treatment regimen provides a new option for sustained virologic response in HCV patients with genotypes 1 or 4 intolerant to or ineligible for interferon-based treatment,” said Thomas Stark, Medical Director, Janssen EMEA.
HCV represents a major global public health concern. There are an estimated nine million people[2] living with HCV in Europe which, if untreated, can cause severe damage to the liver, including cirrhosis and hepatocellular carcinoma (HCC). HCV represents a leading cause of liver transplantation in Europe.[3] Whilst the number of patients being newly diagnosed with HCV is declining, it takes approximately 20 – 30 years for symptoms to appear, with HCV cases expecting to peak between 2030 and 2035.[4],[5]
Dr Andrew Ustianowski, Chair of the British Viral Hepatitis Group and Consultant in Infectious Diseases at North Manchester General Hospital, commented: “The treatment environment in hepatitis C infection is evolving rapidly. Simeprevir is a well-tolerated and efficacious addition to our therapies against hepatitis C, and is a very welcome development for both those with genotype 1 and those with genotype 4.”
The EC marketing authorisation for simeprevir with PegIFN + RBV is based on a clinical trial programme involving three pivotal Phase 3 studies, with over 1000 patients. The trials, QUEST-1, QUEST-2[6] and PROMISE[7], explored the use of simeprevir in combination with PegIFN + RBV in treatment-naïve patients and patients who have relapsed after prior interferon-based treatment. All three studies met their primary endpoints and demonstrated that simeprevir, in combination with PegIFN + RBV, achieves significant sustained virological response rates when compared with PegIFN + RBV alone.
The EC marketing authorisation for the combination of simeprevir and sofosbuvir also contains results from the Phase 2 study, COSMOS, in treatment-naïve patients. This was based upon prior null responder and treatment-naïve patients.[8]
Simeprevir is taken once-daily for 12 weeks, with treatment-naïve and prior-relapser patients receiving pegylated interferon and ribavirin for 24 weeks, and for 48 weeks total by those shown to be prior non-responder patients (including partial and null responders)1. It is generally well tolerated, with the most common adverse events reported in clinical trials (incidence ≥ 5%) including nausea, rash, pruritus, dyspnoea, blood bilirubin increase and photosensitivity reaction.1
In March 2013, simeprevir was approved for the treatment of genotype 1 HCV in Japan, in Canada in September 2013, and the U.S. in November 2013, with the most recent approval occurring in Russia in March 2014. Following the EC marketing authorisation, it is anticipated that simeprevir will be available across a number of European unio countries, in conjunction with reimbursement, in the second half of 2014.
about Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB.
Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorisation held by Janssen-Cilag International NV. Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan, in November 2013 in Canada and the U.S., and in March 2014 in Russia.
EMA批准抗肌营养不良症新药ataluren上市 发布日期：2014-06-02 来源：《费加罗报》
目前，欧洲药品管理局已经批准一种治疗杜氏神经肌肉疾病的新药ataluren(PTC124)，这对于治疗杜氏神经肌肉遗传性疾病为重大进步。
尽管该药不能完全治愈这类疾病，但会明显减缓病情恶化速度。新药将在近期推向市场，给病患带去巨大希望，毕竟治疗该病的药物十分有限。该药由美国PTC疗法研究所开发研制，欧洲药品管理局已准许其在一定条件下进入欧洲市场，但之前必须得到欧盟委员会许可。
杜氏型肌营养不良症是一种儿童最易患的神经肌肉性疾病，且患者几乎仅为男孩。法国平均每3300名儿童中就有1人罹患此病，即每年150到200个新生儿深受其害。杜氏型肌营养不良将导致患者四肢及躯干肌肉日趋无力，以致在青少年时期完全丧失行走能力，最终致患者因心衰竭而早逝。
报道指出，基于“基因手术”这一创新技术，ataluren对于13%的杜氏型肌营养不良患者产生了疗效。这部分患者携带一种特殊的突变基因。这种突变基因过早阻碍了抗肌萎缩蛋白合成，该蛋白对于保证肌肉正常机能不可或缺。通过服用该药物，细胞组织将忽略上述突变基因发出的“终止信号”，从而完成蛋白质的合成。
为证明药效，美国PTC疗法研究所对约200名确诊患病但还能行走的5岁以上儿童进行了多项试验。实验证实，该药的确可以减缓疾病恶化速度，甚至改善行走能力。法国相关肌肉学研究所医疗及科学部门高层托马斯 沃伊特在接受《费加罗报》采访时表示，如果没有药物治疗，上述儿童在6分钟内的移动距离平均每年会减少40米。然而，服用ataluren一年的患儿在6分钟内的移动距离仅减少了30米，这无疑是巨大进步。
强生携手Aduro癌症疫苗技术扩大发展前列腺癌项目 发布日期：2014-06-03 来源：fiercebiotech
最近强生公司忙碌的交易团队们又在加利福尼亚州敲定了另一项研发协议，这次瞄准了伯克利生物技术开发的新技术，该技术被用于前列腺癌疫苗的研发。这次交易包括获得一项曾有失败历史的癌症疫苗计划的权利，最近该计划又产生了一些积极的试验结果。
强生公司创新中心的一次新的交易瞄准了Aduro生物技术药物开发平台的一项申请中的新药，该药用于激发免疫反应。该平台技术使用减毒双缺失型李斯特菌菌株刺激机体产生对抗肿瘤的抗体。
Aduro没有确定最终交易额，但整个交易阶段及前期投入预计高达3.65亿美元，其中大部分集中在后期。
交易的第二部分围绕于GVAX。BioSante 花了很大力气却没能证明疫苗可对抗癌症，Aduro随即获得GVAX的权利。早在2008年关于GVAX的一个后期研究中，实验中治疗组患者比化疗组患者更快死亡，研究立刻被叫停。Aduro把GVAX与另一个产品相结合用于胰腺癌治疗，今年一月得到了一些阳性结果。
现在，强生公司收购GVAX并将其专门用于前列腺癌的治疗研究。虽然在临床上这个癌症疫苗不能单独进行治疗，但在癌症研究领域，该药物给研究者和分析师们一种强烈的感觉，该药将在联合疗法中起重要的作用。
“我们很高兴能为强生提供新的免疫技术，” Aduro首席执行官Isaas在声明中表示，“我们相信这将是我们平台战略的一次重要的验证，我们很高兴能携手强生开发团队率先推进前列腺癌治疗计划。另一方面，我们期待旗下的LADD平台能够研发出更多肿瘤治疗方案。”
J&J expands prostate cancer program with cancer vax tech from Aduro
Johnson & Johnson's ($JNJ) busy deal team in California has nailed down another development pact--this time zeroing in on new technology at a Berkeley biotech that will be used to expand its considerable efforts on prostate cancer R&D. And the deal includes rights to a failed cancer vaccine program which has recently sparked some positive trial results in a follow-up effort aimed at salvaging the work.
This new deal from the J&J Innovation center zeroes in on a pact to license therapeutic candidates from Aduro BioTech's drug development platform, which is focused on kicking up an immune response. The platform tech involves the use of live-attenuated double deleted Listeria monocytogenes strains to spawn the antigens needed to provoke an immune system attack on cancer.
Aduro didn't break down the dollars in the deal, but the whole package of milestones and an upfront tallies up to $365 million, most of which is likely back ended.
The second part of their deal revolves around GVAX. Aduro obtained the rights to GVAX after BioSante($BPAX) failed rather spectacularly in its effort to prove that the therapeutic vaccine could fight cancer. A late-stage study with GVAX was halted back in 2008 after patients in the therapeutic arm began dying at a faster pace than the patients in the chemo arm. Aduro combined GVAX with another one of its pipeline drugs and reported some positive results from a mid-stage study for pancreatic cancer in January.
Now J&J is following up by obtaining the rights to GVAX to use specifically for prostate cancer. Cancer vaccines have failed to impress analysts repeatedly in the clinic as a monotherapy, but there is a strong feeling in some cancer research circles that they can serve an important role in combination therapies.
The deal underscores J&J's commitment to prostate cancer. The pharma giant has been changing the standard of care with Zytiga, and recently bought out Aragon in a billion-dollar deal to get its hand on a second-gen therapy.
"We are pleased to provide Janssen with novel immunotherapies engineered specifically for this indication," said Aduro CEO Stephen Isaacs in a statement. "We believe this is an important validation of our platform strategy and we are excited to have the Janssen development team taking the lead in advancing the prostate cancer program. Separately, we look forward to continued progress with our LADD platform in a broad array of other oncology indications, including pancreatic cancer, mesothelioma, non-small cell lung cancer and glioblastoma among others."
免疫疗法成了本届年会的焦点。除了领先的Pembrolizumab（默克）和Nivolizumab（施贵宝），罗氏和阿斯列康的PD-1,PD-L1抑制剂也进入投资者视野。免疫疗法除了在黑色素瘤、肺癌、和肾癌这些早期适应症之外，在膀胱癌、头颈癌等其它实体瘤也显示一定疗效。虽然这些实体瘤的应答率较低，在10-20%之间，但这些是严重的疾病，几乎没有什么治疗手段，所以任何微小的进展都是值得关注的。但是免疫疗法显然最合适的适应症是黑色素瘤，Nivolizumab和Yervoy的复方组合令88%的患者生存期超过两年，Pembrolizumab也显示相似疗效。免疫疗法在非小细胞肺癌也在小型临床实验中显示生存疗效。现在专家估计免疫疗法的市场总值可达250-350亿美元。但是，免疫疗法也显示比较严重的副作用，尤其是作为复方组合。根据适应症的不同，免疫疗法需和不同的化疗或靶向疗法组合，而有一些组合看来毒性太大，疗效一般，所以免疫疗法到底能在多少肿瘤起到重要作用还有待观察。另外现在公布的数据多是小型实验的应答率，最后多少能在大型临床实验中转化成生存率还存在不少变数。尤其是现在癌症患者对免疫疗法寄予众望，临床实验可能得允许交叉用药，使生存率的测定复杂起来。最后无进展生存期可能会成为主要的临床终点。
礼来的ramucirumab被多数专家认为是个失败。虽然该产品已经上市用于治疗胃癌，并在非小细胞癌症的三期临床实验显示统计学显著的生存期延长。但由于疗效一般，生存期和无进展生存期都仅延长不到两个月，而其预测价格每个疗程可达90000美元，令不少人说正是这些高价鸡肋药物消耗了医疗支出，令象sovaldi这样真正的创新药物得不到应有的回报。但是生命的价值难以界定。今年美国临床专家工作组讨论延长多少寿命才算对病人有意义。对于转移性肺癌，专家认为一线药物应延长3-4个月寿命。按照这个标准ramucirumab确实未能达标，但ramucirumab是作为二线药物，这时病人的选择已经不多，应答率也很差，所以1.4个月寿命的延长也并非微不足道。另外ramucirumab对鳞状细胞和非鳞状细胞亚型疗效相似，而贝伐单抗不能用于鳞状细胞亚型。业界对ramucirumab的负面态度和对免疫疗法的满腔热情形成鲜明对比，虽然后者在多数适应症尚未现示任何生存期疗效。
另一个重要报告是葛兰素的乳腺癌药物Tykerb的ALTTO实验。这是一个8381人的超大型临床实验，全球共有44个国家的946个医疗中心参与。主要比较Tykerb和赫赛汀的区别。实验共有4组，Tykerb单方组已经在两年前因为疗效原因停止。但本次会议公布的结果显示Tykerb和赫赛汀的复方组合未能比赫赛汀单方显示更高的无进展生存率。积极的解释是赫赛汀自己就足以控制乳腺癌，消极的解释是如果控制不好加上Tykerb也无济于事。不管如何，葛兰素已经将该产品卖给诺华，所以今天晚上诺华的高层将有一个不眠之夜。Tykerb是HER2和EGFR的双靶点抑制剂，理论上应有更好疗效，但实际情况显然更复杂。赫赛汀也是HER2抑制剂但是和细胞外部分结合，所以机制略有不同。Tykerb和赫赛汀的复方组合曾增加乳腺癌手术前的病理应答率，但这个替代指标显然未能转化成病人更关心的无进展生存率。这也令以后想以应答率为疗效终点快速申请上市抗癌药的审批难度有所增加。
癌症是个非常复杂的疾病，任何微小的进展都需要巨大的努力，但是治疗手段还是不断在改进。除了免疫疗法，还有一些新的靶向疗法、抗体药物偶联物、血管生成抑制剂等新机理药物显示很好前景。希望现在的星星之火会在未来形成燎原之势。
|手机版|药群论坛
( 蜀ICP备15007902号 )
收藏
支持
反对