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7月药物资讯分享----汤森路透

已有 3475 次阅读 2016-7-22 09:48 |个人分类:药学研究|系统分类:科研笔记


许老师,您好!

一直坚信平凡的小事坚持做会带来不平凡的收获,又到了与您分享药物资讯的时候了,希望这份坚持对您有帮助,本期分享向您汇报几个消息:

1. 汤森路透已经签署一项最终协议,将旗下的知识产权与科技业务以35.5亿美元的价格售予Onex公司和霸菱亚洲投资基金(Baring Private Equity Asia)。

      Onex 公司和霸菱亚洲投资基金承诺,新的公司将会对知识产权与科技业务加大投入,不断支持我们的客户并实现快速增长。我们可以非常肯定地向您保证,您将继续得到我们团队一如既往的高质量服务,而且我们提供的满足您需求的产品和服务也将更为强大。

      汤森路透将继续拥有并运营知识产权与科技业务直到交易完成,该交易预计将在2016年下半年最终交付完成。我们会尽可能地让您了解最新进展.

关于业务该变化,不会影响我们本地对数据库的维护和业务拓展,有任何与汤森路透相关的事务请继续与我联络。

2. 本月2日是我入职汤森路透四周年的日子,时光如梭,4年前刚毕业踏入工作岗位,对新工作的迷茫与热情依然历历在目,4年已过,谢谢您一直的支持与信任,我也一直如初恋般的喜欢着这份工作,继续着我的热情。

3. 本期分享包括:

1)6月药物快讯(见邮件正文)

2)白皮书《肿瘤免疫在希望之光中前行:当前药物研发的机制、策略及方法

3)《进入欧美仿制药市场的成功策略》PPT+录音

4)《全球抗体药物研发进展对中国的启示》PPT

2)3)4)请回复邮件索取,或者查看我们的微信公众号。

每月药物快讯-20166

癌症 CANCER

2016613日,韩美制药在韩国推出OLMUTINIB

olmutinib上个月通过批准后(见2016518日,汤森路透药物新闻),韩美制药在南韩上市该药。勃林格殷格翰享有该药的全球授权(除韩国和中国),此前曾进行全球范围的临床试验(ELUXA 1ClinicalTrazil编号:NCT02485652(韩美制药新闻稿)。

HANMI PHARMACEUTICAL LAUNCHES OLMUTINIB IN SOUTH KOREA

Following approval of the drug last month (see Thomson Reuters Drug News, May 18, 2016), Hanmi Pharmaceutical has launched olmutinib (Olita[R]) in South Korea. Boehringer Ingelheim, which has global rights to olmutinib (with the exception of Korea and China), previously announced its global clinical trial (ELUXA 1; ClinicalTrials.gov Identifier NCT02485652) (Hamni Pharmaceutical News Release).

201669日,欧盟委员会批准贝伐单抗联合TARCEVA治疗EGFR激活突变的晚期非小细胞肺癌

欧盟批准使用罗氏公司贝伐单抗联合特罗凯(TarcevaR,通用名:erlotinib,厄洛替尼盐酸盐)一线治疗携带表皮生长因子受体(EGFR)激活突变的不可切除性晚期非鳞状非小细胞肺癌(NSCLC)成人患者。一项由中外制药公司进行的关键II期研究(JO25567)评估了贝伐单抗一线用药联合厄洛替尼治疗EGFR激活突变的非鳞状NSCLC的日本患者的安全性和疗效,并与厄洛替尼单药治疗进行对比。来自154例患者的数据显示,接受贝伐单抗联合特罗凯治疗的患者中位无进展生存期比特罗凯单独治疗患者延长6.3个月,疾病进展或死亡的相对风险显著降低46%(中位无进展生存期[PFS]16.0个月vs.9.7个月)。没有观察到临床显著不良事件,且毒性可控。其他临床研究结果也支持两者联用的获益,表明两者联用有效且可耐受(罗氏新闻稿)。

EUROPEAN COMMISSION APPROVES AVASTIN PLUS TARCEVA FOR ADVANCED NSCLC WITH EGFR-ACTIVATING MUTATIONS

The European Commission (EC) has approved the use of Roche's Avastin(R) (bevacizumab) in combination with Tarceva(R) (erlotinib hydrochloride) for the first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations. A pivotal phase II study (JO25567) was conducted by Chugai that assessed the safety and efficacy of first-line bevacizumab in combination with erlotinib compared to erlotinib alone in Japanese patients with advanced non-squamous NSCLC with EGFR-activating mutations. Study data from 154 patients showed that patients who received bevacizumab plus erlotinib lived a median of 6.3 months longer without their disease progressing compared to those who received erlotinib alone, representing a statistically significant 46% reduction in the relative risk of disease progression or death (median progression-free survival [PFS]: 16.0 months versus 9.7 months). No new and clinically significant adverse events were observed and the toxicity profile was shown to be managable. The beneficial effect of bevacizumab plus erlotinib is supported by results of other clinical studies, which showed the combination was effective and tolerable (Roche News Release).


厄洛替尼盐酸盐

201668日,AXUMIN在美国上市

Blue Earth Diagnostics和西门子医疗解决方案的全资子公司PETNET Solutions宣布AxuminTM)([18F]Fluciclovine)注射剂在美国上市。Fluciclovine(18F)是用于影像学检查的放射性药物,用于前列腺特异性抗原(PSA)血液水平升高的疑似复发性前列腺癌男性PET成像筛查与探测。FDA上个月批准Axumin,该药是首个通过FDA批准的用于疑似前列腺癌复发检查的F-18 PET成像药物。Axumin奔月内在美国上市,Blue Earth Diagnostics为西门子PETNET Solutions的制造商和独家经销商(Blue Earth Diagnostics新闻稿)。

AXUMIN NOW AVAILABLE IN U.S.

Blue Earth Diagnostics and Siemens' PETNET Solutions, a wholly owned subsidiary of Siemens Medical Solutions, have announced the commercial availability of Axumin(TM) ([18F]fluciclovine) injection in the U.S. Axumin is a novel molecular imaging agent indicated for use in PET imaging to identify suspected sites of prostate cancer recurrence in men who have elevated blood levels of prostate-specific antigen (PSA) following prior treatment. Axumin was approved by the FDA last month and is the first FDA-approved F-18 PET-imaging agent indicated for use in patients with suspected recurrent prostate cancer. Axumin will be commercially available this month through Blue Earth Diagnostics' manufacturer and exclusive distributor in the U.S., Siemens' PETNET Solutions (Blue Earth Diagnostics News Release).

[18F]Fluciclovine

201666日,欧盟批准AFINITOR用于治疗晚期GI和肺NET

欧盟批准诺华公司AfinitorR)(依维莫司)片剂用于治疗不可切除的或转移性分化良好的(I期或II期)进展性胃肠道(GI)或肺来源的非功能性神经内分泌肿瘤(NET)成人患者。Afinitor是首个通过欧盟所有28个成员国以及冰岛和挪威批准,治疗肺来源NET的药物,也是为数不多的治疗此类GI NET的治疗选择之一。EU批准Afinitor基于一项关键III期研究(RADIANT-4ClinicalTrials.gov编号NCT01524783),该研究对晚期进展性分化良好的GI或肺来源非功能性NET成年患者比较了Afinitor和安慰剂。临床试验的结果显示,Afinitor相比安慰剂能显著降低疾病进展风险达52%。此外,Afinitor延长中位无进展生存期(PFS7.1个月,Afinitor组合安慰剂组的中位PFS分别为11.0个月和3.9个月。该项关键性临床试验中的最常见治疗相关的各种等级不良反应(AE)为口腔炎、腹泻、疲劳、感染、皮疹和外周水肿。最常见治疗相关的3/4AE为口腔炎、腹泻和感染。20162月,FDA批准Afinitor用于治疗成人进展性分化良好的不可切除的、局灶晚期或转移性的肺功能性GI或肺来源NET(参见2016229日,汤森路透药物新闻)。20164月,EMA的人用医药产品委员会(CHMP)对Afinitor片剂提出积极意见,建议其用于治疗不可切除的或转移的分化良好的(I级或II级)非功能性GI或肺来源的进展性NET的成年男性患者,20165月,Afinitor这一适应症通过加拿大批准。世界其他地区的审批正在进行中(诺华新闻稿)。

AFINITOR RECEIVES APPROVAL IN THE E.U. FOR THE TREATMENT OF ADVANCED GI AND LUNG NET

The European Commission has approved Novartis' Afinitor(R) (everolimus) tablets for the treatment of unresectable or metastatic, well-differentiated (grade 1 or grade 2) nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin in adults with progressive disease. Afinitor is the first approved therapy in all 28 member states of the E.U., plus Iceland and Norway, for this type of lung NET, and one of very few treatment options available for this type of GI NET. The E.U. approval of Afinitor was based on efficacy and safety data from a pivotal phase III study (RADIANT-4; (ClinicalTrials.gov Identifier NCT01524783) evaluating Afinitor versus placebo in patients with advanced, progressive, well-differentiated nonfunctional NET of GI or lung origin. The results of the trial demonstrated that Afinitor reduced the risk of disease progression by 52% compared with placebo. Additionally, Afinitor increased median progression-free survival (PFS) by 7.1 months, as the median PFS by central review was 11.0 and 3.9 months in the Afinitor arm and in the placebo arm, respectively. The most common treatment-related, all-grade adverse events (AEs) reported in this pivotal trial were stomatitis, diarrhea, fatigue, infections, rash and peripheral edema. The most common treatment-related grade 3/4 AEs were stomatitis, diarrhea and infections. In February 2016, the FDA approved Afinitor for the treatment of adult patients with progressive, well-differentiated nonfunctional NET of GI or lung origin that are unresectable, locally advanced or metastatic (see Thomson Reuters Drug News, February 29, 2016). In April 2016, the Committee for Medicinal Products for Human Use (CHMP) of the EMA adopted a positive opinion for Afinitor tablets for the treatment of unresectable or metastatic, well-differentiated (grade 1 or grade 2) nonfunctional NET of GI or lung origin in adults with progressive disease, and in May 2016, Afinitor received approval for this indication in Canada. Additional worldwide regulatory filings are currently underway (Novartis News Release).


依维莫司

201661日,欧盟批准IMBRUVICA用于CLL一线治疗

欧盟批准ImbruvicaR)(ibrutinib)用于一线治疗成人慢性淋巴细胞性白血病(CLL),这意味着在201410月批准用于特定CLL患者群治疗的基础上进一步扩展适应症(参见20141020日汤森路透药物新闻)。扩展适应症的决定基于IIIRESONATE-2PCYC-1115)临床试验数据,该数据也被作为FDA批准该药用于一线治疗的基础(ClinicalTrials.gov编号NCT01722487),参见汤森路透药物新闻,201637日)。ImbruvicaPharmacyclics进行美国地区的开发上市,该公司去年被艾伯维收购;Janssen Biotech负责欧洲开发上市,Janssen-Cilag(强生公司下的单元)掌握市场授权(艾伯维新闻稿)。

IMBRUVICA APPROVED IN E.U. AS FIRST-LINE TREATMENT FOR CLL

The European Commission (EC) has approved Imbruvica(R) (ibrutinib) as a first-line treatment for adults with chronic lymphocytic leukemia (CLL), expanding initial EC approval in October 2014 for certain patients with CLL (see Thomson Reuters Drug News, October 20, 2014). The broadened indication was based on data from the phase III RESONATE-2 (PCYC-1115) trial, which also served as the basis for the FDA's approval in the first-line treatment setting (ClinicalTrials.gov Identifier NCT01722487; see Thomson Reuters Drug News, March 7, 2016). Imbruvica was jointly developed and commercialized in the U.S. by Pharmacyclics, which AbbVie acquired last year, and Janssen Biotech. In Europe, Janssen-Cilag, a unit of Johnson & Johnson, holds the marketing authorization (AbbVie News Release).


Ibrutinib

心血管疾病 CARDIOVASCULAR DISORDERS

201667日, FDA批准艾尔健FDC BYVALSON用于治疗高血压

艾尔健称FDA批准Byvalson(TM) (奈必洛尔/缬沙坦)5mg/80mg片剂上市用于降压治疗。药物时首个在美国市场获批的由β受体拮抗剂和血管紧张素II受体拮抗剂组成的固定剂量抗高血压组合药物。本次FDA给予的积极意见主要依据一项为期8周的双盲、安慰剂对照、剂量递增III期临床试验。该试验总共招募了约41001期或2期高血压受试患者。经过为期4周的治疗后,与奈必洛尔或缬沙坦单独给药组相比, Byvalson治疗组患者的自基线血压水平(舒张压和收缩压)显著降低,各组间不良反应事件发生率接近(艾尔健新闻稿)。

FDA APPROVES ALLERGAN'S FDC BYVALSON FOR HYPERTENSION

Allergan said that the FDA has approved Byvalson(TM) (nebivolol and valsartan) 5 mg/80 mg tablets, to treat hypertension by lowering blood pressure. The drug is the first fixed-dose combination (FDC) of a beta-blocker and angiotensin II receptor blocker available in the U.S. The approval was based on a phase III double-blind, placebo-controlled, dose-escalating, 8-week efficacy and safety study in 4,100 patients with stage 1 or 2 hypertension in which treatment with the FDC for 4 weeks demonstrated statistically significant reductions from baseline in diastolic and systolic blood pressure versus either nebivolol alone or valsartan alone (Allergan News Release).


奈必洛尔


缬沙坦

201667日,泰尔茂在日本推出HEARTSHEET

泰尔茂宣布在日本开始销售HeartSheet,一种用于治疗慢性缺血性心脏病引起的严重心力衰竭的细胞和组织的产品。治疗包括通过培养从患者大腿部取得的骨骼肌中含有的成肌细胞,形成骨骼肌骨架层,随后将细胞层转移到患者心脏表面。HeartSheet在日本获得附条件的批准,包括两个工具包,工具包A用于采集患者细胞,工具包B用于培养骨骼肌细胞并得到细胞层。工具包A已经开始向医疗机构出手,并出现第一例报销细胞采集费用的患者。泰尔茂与大阪大学联合推进该项研究,对骨骼肌细胞层的临床研究是新能源和工业技术开发组织(NEDO)赞助项目的一部分。泰尔茂而参与了由东京女子医科大学对使用细胞层的再生医学的研究项目(泰尔茂新闻稿)。

TERUMO LAUNCHES HEARTSHEET IN JAPAN

Terumo has commenced sales in Japan of HeartSheet, a cellular and tissue-based product designed for treating severe heart failure caused by chronic ischemic heart disease. The treatment involves producing skeletal myoblast sheets by culturing skeletal myoblasts contained in muscle tissue that has been taken from the patient's own thigh, and then transplanting the sheets onto the surface of the patient's heart. HeartSheet, which was granted conditional approval in Japan, comprises two kits: Kit A for collecting the patient's cells, and Kit B with cultured skeletal myoblasts and tools for producing sheets from cells. Kit A has already been sold to one medical institution, leading to the first case of patient cell collection covered by health insurance. Terumo has been promoting joint research with Osaka University, where clinical research on skeletal myoblast sheets is underway as part of a project sponsored by the New Energy and Industrial Technology Development Organization (NEDO). Terumo has also participated in a research project, led by Tokyo Women's Medical University, on regenerative medicine using cell sheets (Terumo News Release).

皮肤疾病 DERMATOLOGICAL DISORDERS

2016622日, CHUGAIMARUHO制药推出MARDUOX联合外用软膏治疗寻常型银屑病

Chugai制药和Maruho宣布两家公司将联合推出MarduoxR)软膏(马沙骨化醇/丁酸丙酸倍他米松)用于治疗寻常型银屑病。Marduox是一种外用制剂,含有马沙骨化醇和皮质类固醇丁酸丙酸倍他米松,马沙骨化醇是一种由Chugai开发的维生素D3衍生物。两种药物均可单独或联合用于寻常型银屑病治疗。MarduoxChugaiMaruho联合开发,作为一种使用简便的联合药物,20163月获得市场批准。ChugaiMaruho间的合作始于2001Oxarol®(马沙骨化醇)25 mcg/g软膏上市时(参见2001620日汤森路透药物新闻),2007年推出Oxarol®乳液mcg/gMaruho同样上市了上述两种药物(Chugai制药新闻稿)。

CHUGAI AND MARUHO LAUNCH MARDUOX COMBINATION TOPICAL OINTMENT FOR PSORIASIS VULGARIS

Chugai Pharmaceutical and Maruho announced that both companies have launched Marduox(R) Ointment (maxacalcitol/betamethasone butyrate propionate) for the indication of psoriasis vulgaris. Marduox is a topical preparation that combined maxacalcitol, an active vitamin D3 derivative developed by Chugai, and the corticosteroid betamethasone butyrate propionate. Both drugs are indicated for psoriasis vulgaris and are clinically used individually or together for the treatment of the disease. Marduox was jointly developed by Chugai and Maruho as an easy-to-use combination drug, and acquired the marketing approval in March 2016. The collaboration between Chugai and Maruho started in 2001 with the launch of Oxarol(R) (maxacalcitol) Ointment 25 mcg/g (see Thomson Reuters Drug News, June 20, 2001), and followed by the launch of Oxarol(R) Lotion 25 mcg/g in 2007. Maruho has marketed both of these drugs (Chugai Pharmaceutical News Release).


马沙骨化醇


丁酸丙酸倍他米松

诊断学 DIAGNOSTICS

2016616, QIAGEN推出QIASURE宫颈癌甲基化测试

QIAGEN推出QIAsure甲基化测试,一种新的CE认证的分子诊断试剂,用于检测患者发生宫颈癌的风险。测试计划销往欧洲、中东和亚洲国家市场,预计在今年下半年在欧洲上市。QIAsure甲基化测试是对人乳头瘤病毒(HPV)筛查测试的高度补充,测试后高风险HPV测试或Pap试纸上异细胞学异常的细胞可被用作临床医生收集或收集样本。QIAsure测试通过检测宿主细胞启动子区FAM19A4mir124-2基因的DNA甲基化,为宫颈癌风险提供准确分层,mir124-2基因在宫颈癌发生时高度甲基化,被用作分析中的DNA标记,为患者风险提供可靠检测,辅助监测和治疗决定。该测试通过Rotor-Gene®Q MDx系统验证,该系统属于自动化解决方案分子QIA symphony家族之一。QIAGENSelf-screen合作,Self-screen是荷兰VU大学医学中心的生物技术子公司,从事该测试的开发(QIAGEN新闻稿)。

QIAGEN LAUNCHES QIASURE METHYLATION TEST FOR CERVICAL CANCER

QIAGEN has announced the launch of the QIAsure Methylation Test, a novel CE-marked molecular diagnostic test for use in differentiating patients' risk of developing cervical cancer. The test is launching in Europe, the Middle East and Africa, and is expected to become available in Europe in the later course of this year. The QIAsure Methylation Test is highly complementary to human papillomavirus (HPV) screening tests and follows either a positive high risk HPV test or a finding of abnormal cells in cytology from a Pap smear and can be used on either clinician collected or self-collected samples. QIAsure testing accurately stratifies cervical cancer risk by detecting and measuring DNA methylation in promoter regions of host cell FAM19A4 and mir124-2 genes, which are hypermethylated in cervical cancers. In large-scale studies, the DNA markers used in this assay have demonstrated reliable additional insights into a patient's individual risk and contributed to decisions on surveillance and treatment. The test has been validated on the Rotor-Gene(R) Q MDx system, a PCR platform that is a member of the modular QIA symphony family of automation solution. QIAGEN collaborated with Self-screen, a biotech spinoff company of VU University Medical Center, the Netherlands, in developing this test (QIAGEN News Release).

感染 INFECTIONS

2016629日, FDA批准EPCLUSA单药片剂用于所有基因型的慢性HCV感染

美国FDA宣布批准口服抗丙肝药物Epclusa®sofosbuvir 400 mg/velpatasvir 100 mg)单药用于所有成人慢性1-6型慢性丙肝病毒(HCV)感染。Epclusa还被批准单独用于治疗基因型2型和3型无需利巴韦林治疗的HCV病毒感染。12Epclusa治疗被批准用于治疗无肝硬化或代偿性肝硬化(Child-Pugh A)的患者,而与利巴韦林联用治疗则被批准用于失代偿肝硬化(Child-Pugh BC)患者。EpclusaFDA优先审查项目审查,此前还获得突破性治疗指定。批准基于从国际III期研究ASTRAL-1ASTRAL-2ASTRAL-3ASTRAL-4 (ClinicalTrials.gov编号分别为NCT02201940NCT02220998NCT02201953金和NCT02201901)中获得的数据。ASTRAL-1, ASTRAL-2, ASTRAL-3临床试验中,1,035例无肝硬化或代偿性肝硬化的基因型1-6慢性HCV感染者受试者接受了sofosbuvir/velpatasvir固定组合疗法治疗12周。ASTRAL-4试验中, 267例基因型1-6HCV感染伴随失代偿肝硬化(Child-Pugh B)患者随机分配至接受Epclusa联合或不联合利巴韦林治疗组治疗12周或Epclusa治疗24周组。所有研究的主要终点均为SVR12ASTRAL-1ASTRAL-2ASTRAL-3中接受sofosbuvir/velpatasvir12周治疗的1035例患者中,1015例(98%)受试者在治疗结束后12周获得了SVRASTRAL-4中,接受 Epclusa联合利巴韦林治疗12周组,94%的患者获得SVR12;接受Epclusa治疗12周组,83%的患者获得SVR12;接受Epclusa治疗24周组,86%的患者获得SVR12。头痛和疲劳是最常见的不良反应,ASTRAL-1ASTRAL-2ASTRAL-3试验中sofosbuvir/velpatasvir治疗的(超过10%及以上的)HCV感染患者出现头痛和疲劳。且在安慰剂组治疗患者中发生频率近似或更高。ASTRAL-4研究中,接受sofosbuvir/velpatasvir和利巴韦林联合治疗的87例失代偿肝硬化HCV感染患者中,疲劳、贫血、恶心、头痛、失眠和腹泻是最常见的不良反应(发生率10%及以上)。接受sofosbuvir/velpatasvirsofosbuvir/velpatasvir利巴韦林联合治疗的患者中,分别有两例和四例患者因不良事件中断治疗。Epclusa伴有警告,提示患者和医务人员Epclusa和其它抗病毒药物联合使用可能引起症状性心动过缓,同时使用胺碘酮联合其他HCV直接抗病毒药物的患者甚至需要起搏器治疗。此外,Epclusa伴有的另外一个警告是避免同时使用能降低Epclusa的血药浓度的药物,该药物会降低Epclusa的疗效。美国Diplomat药房宣称将开始销售Epclusa。吉利德11家印度生产合作商已经获得该药授权,目前开始向101个发展中国家生产和销售该药的仿制药(吉利德新闻稿;FDA新闻稿;Diplomat药房新闻稿)。

FDA APPROVES EPCLUSA AS PAN-GENOTYPIC SINGLE-TABLET REGIMEN FOR CHRONIC HCV INFECTION

The FDA has approved Gilead Sciences' Epclusa(R) (sofosbuvir 400 mg/velpatasvir 100 mg), the first all-oral, pan-genotypic, single-tablet regimen for the treatment of adults with genotype 1-6 chronic hepatitis C virus (HCV) infection. Epclusa is also the first single-tablet regimen approved for the treatment of patients with HCV genotype 2 and 3 without the need for ribavirin. Epclusa for 12 weeks was approved in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A), and in combination with ribavirin for patients with decompensated cirrhosis (Child-Pugh B or C). Epclusa was reviewed under the FDA's priority review program, having also previously received breakthrough therapy designation. Approval was supported by data from four international phase III studies, ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4 (respective ClinicalTrials.gov Identifiers NCT02201940, NCT02220998, NCT02201953 and NCT02201901). In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,035 patients with genotype 1-6 chronic HCV infection, without cirrhosis or with compensated cirrhosis received 12 weeks of sofosbuvir/velpatasvir. The ASTRAL-4 study randomized 267 patients with genotype 1-6 HCV infection, with decompensated cirrhosis (Child-Pugh B), to receive 12 weeks of sofosbuvir/velpatasvir with or without ribavirin or 24 weeks of sofosbuvir/velpatasvir. The primary endpoint for all studies was SVR12. Of the 1,035 patients treated with sofosbuvir/velpatasvir for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98%) achieved SVR12. In ASTRAL-4, patients with decompensated cirrhosis receiving sofosbuvir/velpatasvir with ribavirin for 12 weeks achieved a high SVR12 rate (94%) compared to those who received sofosbuvir/velpatasvir for 12 weeks or 24 weeks (83% and 86%, respectively). Headache and fatigue were the most common adverse reactions (10% or greater) experienced by HCV-infected patients treated with sofosbuvir/velpatasvir in ASTRAL-1, ASTRAL-2 and ASTRAL-3 and occurred at a similar or higher frequency in placebo-treated patients. In the 87 HCV-infected patients with decompensated cirrhosis treated with sofosbuvir/velpatasvir and ribavirin in the ASTRAL-4 study, fatigue, anemia, nausea, headache, insomnia and diarrhea were the most common adverse reactions (10% or more). Two and four patients treated with sofosbuvir/velpatasvir and sofosbuvir/velpatasvir with ribavirin respectively discontinued treatment due to adverse events. Epclusa carries a warning regarding reports of symptomatic bradycardia and cases requiring pacemaker intervention when amiodarone is used with sofosbuvir in combination with another HCV direct-acting antiviral. It also carries a warning not to use with certain drugs that may reduce the amount of sofosbuvir/velpatasvir in the blood, which could lead to reduced efficacy. In the U.S., Diplomat Pharmacy announced that it will be dispensing Epclusa. Epclusa is already licensed to Gilead's 11 Indian manufacturing partners who may now begin production and distribution of a generic version of this medicine for 101 developing countries (Gilead Sciences News Release; FDA News Release; Diplomat Pharmacy News Release).


Sofosbuvir


Velpatasvir

2016628 SPERO THERAPEUTICS推出抗铜绿假单胞菌感染新型MVFR抑制剂

Spero Therapeutics的科学家们开发出一种新的多毒力因子调节剂(MvfR)抑制剂,对铜绿假单胞菌感染有效。先导化合物SPR-00305可显著抑制MvfR通路,对PA144羟基2庚基喹啉(HHQ)、绿脓菌素(PYO)和34-二羟基-2 heptoquinolinePQS)的IC50分别为115 nM93 nM109 nM。进一步测试该化合物对免疫功能正常的急性大腿感染模型的作用。与溶剂对照相比,该化合物可分别降低PQSHHQ50%40%。在中性粒细胞减少的急性大腿感染模型中,SPR-00305口服给药(200 mg)引起HHQ水平轻微下降。综合结果看,SPR-00305是强效MvfR抑制剂且表现与靶点结合(Rubio, A. et al. 56th Intersci Conf Antimicrob Agents Chemother (ICAAC),(616-20日,波士顿),2016年,FRIDAY-483摘要)。

SPERO THERAPEUTICS PRESENTS NEW MVFR INHIBITOR FOR P. AERUGINOSA INFECTIONS

Scientists from Spero Therapeutics have developed new multiple virulence factor regulator (MvfR) inhibitors reported to be useful for Pseudomonas aeruginosa infections. The lead compound, SPR-00305, potently inhibited the MvfR pathway with IC50s of 115 nM against 4-hydroxy-2-heptylquinoline (HHQ), 93 nM against pyocyanin (PYO) and 109 nM against 3,4-dihydroxy-2-heptoquinoline (PQS) in PA14. The compound was further tested in the immunocompetent acute thigh infection model. It decreased PQS by 50% and HHQ by 40% in comparison with vehicle. In the neutropenic acute thigh infection model, SPR-00305 oral administration (200 mg) resulted in a slight decrease in HHQ levels. Taken together, these results suggest that SPR-00305 is a potent MvfR inhibitor and displays target engagement (Rubio, A. et al. 56th Intersci Conf Antimicrob Agents Chemother (ICAAC) (June 16-20, Boston) 2016, Abst FRIDAY-483).


SPR-00305

2016627日,赛诺菲巴斯德VAXIGRIPTETRA疫苗获欧盟上市评审

赛诺菲发布消息称,赛诺菲巴斯德疫苗部分完成四价流感疫苗VaxigripTetra(TM)审批,从德国参考成员国家埃利希保罗研究所得到积极结果,完成该欧洲分立流程。目前可在参考成员国家(德国)和参与该流程的所有成员国家申请上市。VaxigripTetra是一种四价流感疫苗,包括两种A菌株(A/H1N1A/H3N2)和两种B型菌株(B/VictoriaB/Yamagata),用于年龄36个月及以上人群(赛诺菲新闻)。

REGULATORY DOSSIER FOR SANOFI PASTEUR'S VAXIGRIPTETRA APPROVED IN EUROPE

Sanofi said its Sanofi Pasteur vaccines division disclosed that its quadrivalent influenza vaccine, VaxigripTetra(TM), obtained a positive end of procedure from the German Reference Member State Paul Ehrlich Institute, as a conclusion of the European decentralized procedure. Marketing authorizations can now be issued in the reference member state (Germany) and each of the concerned member states involved in the procedure. VaxigripTetra is a four-strain influenza vaccine, containing two A strains (A/H1N1 and A/H3N2) and two B strains (B/Victoria and B/Yamagata), for use in individuals, ages 36 months or older (Sanofi News Release).

2016613日, FDA批准VAXCHORA霍乱疫苗

美国食品和药物管理局在优先审查后批准Vaxchora单剂量口服活霍乱疫苗霍乱疫苗用于减轻18-64周岁成年人群。Vaxchora是唯一一种被FDA批准用于预防霍乱的疫苗,预计该疫苗将在今年第三季度上市。Vaxchora是一种用于主动免疫对抗霍乱弧菌血清型O1感染的口服疫苗。其中使用的减毒霍乱疫苗株为CVD 103-HgR2010年从马里兰大学医学院疫苗开发中心(UM SOM2010年授权。UM SOMPaxVax合作进行Vaxchora开发。一项随机分组安慰剂对照的挑战性研究证实了该疫苗的效果,研究包括197例美国志愿者,年龄在1845周岁。197例志愿者中,68人接受Vaxchora66例接受安慰剂给药,并感染霍乱弧菌。Vaxchora接种后的10天内,对90%的感染有效,接种后3个月内对79%的感染有效。研究中对有症状的患者进行补液和给予抗生素。两项安慰剂对照的研究中评估了受试者对疫苗的免疫响应,研究对美国和澳大利亚成年受试者进行,年龄在18-64周岁。参与组年龄在18-45周岁,93%Vaxchora接种者产生对霍乱有效的抗体。46-64周岁年龄组中,90%产生对霍乱有效的抗体。在四项随机分组安慰剂对照的多中心研究中,对18-64周岁成年受试者评估Vaxchora的安全性,接受疫苗的受试者达3235例,对照组562例给安慰剂。接种疫苗人群中随常见副作用包括疲劳、头痛、腹痛、恶心、呕吐、食欲减退和腹泻。PaxVax还开始了对其他人群接种该疫苗的研究,如儿童和居住在霍乱疫区的人群(PaxVax新闻;FDA新闻)。

FDA APPROVES VAXCHORA CHOLERA VACCINE

The FDA has approved PaxVax's Vaxchora(TM), a single-dose oral, live attenuated cholera vaccine for use in adults aged 18-64 years, following a priority review. Vaxchora is the only vaccine available in the U.S. for protection against cholera and the only single-dose vaccine for cholera currently licensed anywhere in the world. The vaccine is expected to become commercially available in the third quarter of this year. Vaxchora is an oral vaccine indicated for active immunization against disease caused by Vibrio cholera serogroup O1. The attenuated cholera vaccine strain used in Vaxchora is CVD 103-HgR, which was in-licensed from the Center for Vaccine Development at the University of Maryland School of Medicine (UM SOM) in 2010. Collaborators at UM SOM worked with PaxVax on the development of Vaxchora. Vaxchora's efficacy was demonstrated in a randomized, placebo-controlled challenge study of 197 U.S. volunteers aged 18-45 years. Of the 197 volunteers, 68 Vaxchora recipients and 66 placebo recipients were challenged by oral ingestion of V. cholera. Vaxchora efficacy was 90% among those challenged 10 days after vaccination and 79% among those challenged 3 months after vaccination. The study included provisions for administration of antibiotics and fluid replacement in symptomatic participants. Two placebo-controlled studies to assess the immune system's response to the vaccine were also conducted in the U.S. and Australia in adults aged 18-64 years. In the group of participants aged 18-45 years, 93% of Vaxchora recipients produced antibodies indicative of protection against cholera. In the group aged 46-64 years, 90% produced antibodies indicative of protection against cholera. The safety of Vaxchora was evaluated in adults aged 18-64 years in four randomized, placebo-controlled, multicenter trials in which 3,235 study participants received Vaxchora and 562 received a placebo. The most common adverse reactions reported by Vaxchora recipients were tiredness, headache, abdominal pain, nausea/vomiting, lack of appetite and diarrhea. PaxVax has also begun development programs for the vaccine in additional populations, such as children and people living in countries affected by cholera (PaxVax News Release; FDA News Release).

201667日, VONOSAPVONOPION获日本批准用于根除幽门螺杆菌

日本制药巨头武田(Takeda)与大冢制药(Otsuka)克日公布,日本卫生劳动福利部(MHLW)已核准VONOSAPvonoprazan延胡索酸、阿莫西林和克拉霉素)pak 400Vonosap pack 800连同Vonopion(R) (vonoprazan延胡索酸、阿莫西林和甲硝唑) pack用于革除幽门螺杆菌(H.pylori eradication)。VONOSAP是一种三药罩泡包装产物,结合武田制药开发的钾竞争酸阻滞剂takecabR)(vonoprazan富马酸)片剂,阿莫林(R)(阿莫西林)胶囊和ClarithromycinR)(克拉霉素),是用于幽门螺杆菌主要根除的片剂。Vonopion是一种三药罩泡包装产品,包括TAKECAB片剂(vonoprazan fumarate,富马酸沃诺拉赞,一种酸抑制剂)、Amolin胶囊(amoxicillin,阿莫西林)、Clarith片剂(clarithromycin,克拉霉素),用于继发幽门螺杆菌根除治疗。这些产品还均可被用于幽门螺杆菌感染与胃溃疡、十二指肠溃疡、胃黏膜淋巴瘤、特发性血小板减少性紫癜,内镜下胃切除术后早期胃癌和幽门螺杆菌胃炎的治疗。武田制药和大冢制药将基于2014年签署的日本合作推广协议进行经销活动(武田制药和大冢制药新闻)。

VONOSAP AND VONOPION PACKS LAUNCHED IN JAPAN FOR H. PYLORI ERADICATION

Takeda Pharmaceutical and Otsuka Pharmaceutical have announced the availability in Japan of Vonosap(R) (vonoprazan fumarate, amoxicillin and clarithromycin) pack 400 and Vonosap pack 800, together with Vonopion(R) (vonoprazan fumarate, amoxicillin and metronidazole) pack for Helicobacter pylori eradication. Vonosap is a triple-drug blister pack combining the potassium-competitive acid blocker Takecab(R) (vonoprazan fumarate) tablet developed by Takeda, Amolin(R) (amoxicillin) capsule and Clarith(R) (clarithromycin) tablet for primary eradication of H. pylori. Vonopion is a triple-drug blister pack containing Takecab, Amolin and Fragile(R) (metronidazole) tablet for secondary eradication of H. pylori. The packs are all indicated for use in treating H. pylori infection in patients with gastric ulcers, duodenal ulcers, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, following endoscopic resection of the stomach in early-stage gastric cancer, and in H. pylori gastritis. Takeda Pharmaceutical and Otsuka Pharmaceutical will conduct promotional activities under a Japanese copromotion agreement signed in 2014 (Takeda Pharmaceutical and Otsuka Pharmaceutical News Release).

201661日, TEFLAROFDA批准用于儿童感染治疗

FDA已批准艾尔健(Allergan)为抗生素产品Teflaroceftaroline fosamil)新适应症递交的补充NDAsNDA),用于2个月至18岁以下的儿科患者,治疗急性细菌性皮肤及皮肤组织感染(ABSSSI),包括由耐甲氧西林金黄色葡萄球菌(MRSA)引起的感染,以及由肺炎链球菌和其他敏感菌导致的社区获得性细菌性肺炎(CABP)。Teflaro新适应症的获批,是基于评估Teflaro治疗儿科患者(2个月-18岁以下)的临床研究数据,包括治疗ABSSSI的一项主动控制研究和治疗CABP2项主动控制研究。在ABSSSI主动控制研究中,Teflaro的疗效和安全性与万古霉素(vancomycin)或头孢唑林(cefazolin)(两者均可选择与氨曲南联用)媲美。在CABP研究中,Teflaro疗效与头孢曲松(ceftriaxone)进行比较。在儿科患者中使用Teflaro是基于Teflaro治疗成人的丰富和充分对照研究,以及儿科群体试验中获得的额外药代动力学和安全性数据。儿科ABSSSI试验中,对治疗意向人群(MITT)中ABSSSI159例患者评估Teflaro疗效。研究第3Teflaro治疗患者表现响应率高于对照组,临床缓解率分别为80.4%75%。试验治疗(TOC)随访(治疗结束后815天)时Teflaro和对照组的临床治愈率分别为94.4%86.5%。为评估Teflaro的治疗效果,CABP试验中,对MITT人群中143CABP患者进行分析。研究第4Teflaro和对照组的临床缓解率分别为69.2%66.7%TOCTeflaro和对照品的临床治愈率分别为87.9%88.9%。这些儿科研究中,Teflaro临床研究剂量对ABSSSICABP治疗的安全性特征相似。安全性发现与成人研究中发现类似,没有发现已知头孢菌素类作用以外的安全性问题。Teflaro是首个且唯一获批用于成人和儿科(2个月以上)群体治疗疑似病原菌引起ABSSSICABP的头孢菌素,给药时间5分钟至1小时,经静脉注射给药(艾尔健新闻稿)。

FDA APPROVES TEFLARO IN PEDIATRIC PATIENTS

The FDA has approved Allergan's supplemental NDA (sNDA) for Teflaro(R) (ceftaroline fosamil), granting new indications for pediatric patients 2 months of age to less than 18 years of age with acute bacterial skin and skin structure infections (ABSSSI), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired bacterial pneumonia (CABP) caused by Streptococcus pneumoniae and other designated susceptible bacteria. These new indications were approved on the basis of results from clinical studies evaluating Teflaro in pediatric patients (2 months to less than 18 years of age), including one active-controlled study in ABSSSI and two active-controlled studies in CABP. In the ABSSSI active-controlled study, the efficacy and safety of Teflaro was compared with that of vancomycin or cefazolin (each with optional aztreonam), and in the CABP studies, Teflaro was compared with ceftriaxone. Use of Teflaro in pediatric patients is supported by evidence from adequate and well-controlled studies of Teflaro in adults, as well as additional pharmacokinetic and safety data from pediatric trials. To evaluate the treatment effect of Teflaro in the pediatric ABSSSI trial, an analysis was conducted in 159 patients with ABSSSI in the modified intent-to-treat (MITT) population. Patients treated with Teflaro demonstrated a higher response at study day 3 versus the comparator group, with clinical response achieved in 80.4 and 75% of patients, respectively. Clinical cure rates at the test of cure (TOC) visit (8 to 15 days after the end of therapy) for the ABSSSI pediatric trial were 94.4% for patients treated with Teflaro and 86.5% for the comparator. To evaluate the treatment effect of Teflaro in the CABP trial, an analysis was conducted in 143 patients with CABP in the MITT population. The clinical response at study day 4 was 69.2% for patients treated with Teflaro and 66.7% for the comparator. Clinical cure rates at TOC were 87.9% for patients treated with Teflaro and 88.9% for the comparator. In these pediatric patient studies, Teflaro demonstrated a safety profile that was compatible with treatment of ABSSSI and CABP at the clinical dosages studied. The safety findings were similar to those seen in the adult studies, and no safety concerns were identified beyond those already known to be cephalosporin class effects. Teflaro is the first and only cephalosporin indicated in adults and pediatric patients 2 months of age and older for the treatment of ABSSSI and CABP due to designated susceptible pathogens that can be administered by intravenous infusion in 5 minutes to 1 hour (Allergan News Release).


头孢洛林醋酸酯

代谢性疾病 METABOLIC DISORDERS

2016627日,胰淀素类似物ZP-4982ZP-5461可改善糖尿病模型中的血糖控制

Zealand PharmaZucker雄性胰岛素肥胖大鼠中,对两种长效胰淀素类似物ZP-4982ZP-5461的抗胰岛素作用进行评估。ZP-4982给药剂量为30 nmol/kg s.c.,每5天一次,ZP-5461给药剂量为3, 30100 nmol/kg s.c.,每5天给药一次。一组动物同时接受利拉鲁肽给药,给药剂量为40 nmol/kg s.c. b.i.d。与溶剂治疗组相比,积极治疗可减少动物摄食量和饮水量。ZP-4982ZP-5461可降低非空腹血糖、空腹血糖水平和末端HbA1c水平。腹腔内葡萄糖耐量试验中,药物较溶剂对照显著改善葡萄糖耐量。ZP-5461测试剂量30 nmol/kg下可改善控制饮食的对照组动物的葡萄糖控制,提示药物具有抗糖尿病作用(Skarbaliene, J. 76th Annu Meet Sci Sess Am Diabetes Assoc (ADA)610-14日,新奥尔良,2016摘要 283-LB)。

LONG-ACTING AMYLIN ANALOGUES ZP-4982 AND ZP-5461 IMPROVE GLYCEMIC CONTROL IN DIABETES MODEL

Zealand Pharma has evaluated the antidiabetic effects of two long-acting amylin analogues, ZP-4982 and ZP-5461, in male Zucker diabetic fatty rats. ZP-4982 was administered at 30 nmol/kg s.c. every 5 days while ZP-5461 was administered at 3, 30 and 100 nmol/kg s.c. every 5 days. One group of animals also received liraglutide was given at 40 nmol/kg s.c. b.i.d. The active treatments reduced food and water intake in the animals compared to vehicle treatment. Non-fasting and fasting blood glucose levels and terminal HbA1c were decreased by ZP-4982 and ZP-5461. The agents also significantly improved glucose tolerance compared to vehicle during an intra-peritoneal glucose tolerance test. ZP-5461 at 30 nmol/kg improved glycemic control more than in food-restricted pair-fed animals, indicating antidiabetic drug effects (Skarbaliene, J. 76th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (Jun 10-14, New Orleans) 2016, Abst 283-LB).

201661日, AMICUS药物MIGALASTAT盐酸盐首次通过欧盟批准

欧盟全面批准Amicus医药的口服小分子伴侣药物GalafoldTM)(Migalastat盐酸盐)作为一线疗法以用于长期治疗法布雷病成人和年龄在16岁及以上的青少年患者,患者需经确诊为法布里病(α-半乳糖苷酶缺陷疾病)且携带可治疗突变(amendable mutation)。公司对德国销售该产品,计划将该治疗纳入其他欧洲国家的医疗法案报销范围。Galafold的标签适应症包括269种已被鉴定并确定为有关联的GLA突变。这269种突变代表了目前诊断为法布里病的人群的35%50%Amicus Therapeutics新闻稿)。

AMICUS'S MIGALASTAT HYDROCHLORIDE OBTAINS FIRST APPROVAL IN EUROPE

The European Commission has granted full approval to Amicus Therapeutics' oral small-molecule chaperone Galafold(TM) (migalastat hydrochloride) as a first-line therapy for long-term treatment of adults and adolescents, aged 16 years and older, with a confirmed diagnosis of Fabry's disease (alpha-galactosidase A deficiency) who have an amenable mutation. The company is supplying the product in Germany and plans to begin the reimbursement process with healthcare authorities in the other major European countries. Galafold's label includes 269 Fabry-causing mutations, representing 35-50% of patients with Fabry disease (Amicus Therapeutics News Release).


Migalastat hydrochloride

肾泌尿系统疾病 RENAL-UROLOGIC DISORDERS

2016621日,FDA批准RAYALDEE治疗慢性肾脏病继发性甲状旁腺功能亢进

Rayaldee(R)calcifediol 30 mcg)已获FDA批准用于治疗慢性肾脏病(CKD3-4期维生素D缺乏(血清总25-羟维生素D水平<30 ng/mL)相关的成人继发性甲状旁腺功能亢进。Opko Health预计今年下半年将Rayaldee推向美国市场。Rayaldee具有专利保护配方设计,用于升高总血清25-羟维生素D水平(激素原)到目标水平(至少30 ng/mL)及减少甲状旁腺甲状旁腺激素(iPTH)升高。FDA批准该药的依据来自于2项为期26周的双盲、III期、安慰剂对照试验结果。试验表明,与安慰剂组相比,接受Calcifediol治疗的大多数CKD 3期或4期伴维生素D不足的SHPT患者血清甲状旁腺激素可降低30%或以上,或血浆iPTH降低水平较安慰剂组更为显著(ClinicalTrials.gov编号NCT01651000NCT01704079)。Calcifediol组维生素D不足得到纠正者超过80%,而安慰剂组少于7%Calcifediol组患者平均血清钙,磷水平比安慰剂组患者增加0.1 mg/dL,但研究者认为该变化无临床意义。研究者发现,接受治疗的CKD 3期或4期患者间的有效性和安全性无统计学差异(Opka Health新闻稿)。

FDA APPROVES RAYALDEE FOR SECONDARY HYPERPARATHYROIDISM IN CKD

The FDA has approved Rayaldee(R) (calcifediol 30 mcg) extended-release capsules for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Opko Health expects to launch Rayaldee in the U.S. in the second half of this year. Rayaldee has a patented formulation designed to raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) and to reduce elevated intact parathyroid hormone (iPTH). Results from two 26-week, placebo-controlled, double-blind phase III trials demonstrated that a larger proportion of stage 3 or 4 CKD patients with secondary hyperparathyroidism and vitamin D insufficiency achieved 30% or greater reductions in plasma iPTH when treated with calcifediol than with placebo (ClinicalTrials.gov Identifiers NCT01651000 and NCT01704079). Vitamin D insufficiency was corrected in more than 80% of the patients receiving calcifediol compared with less than 7% of subjects receiving placebo. Mean serum calcium and phosphorus levels increased by 0.1 mg/dL during calcifediol treatment compared to placebo treatment, but these changes were deemed clinically irrelevant. No differences in calcifediol's efficacy or safety were observed between patients with stage 3 CKD or stage 4 CKD (Opko Health News Release).


Calcifediol

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Jingzhi Li(李敬芝)

IP & Science

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