Bento Lab
Bento Lab
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便当实验室
作者：
K. Aydin;Ç. Okuyaz;Kvlcm Gücüyener;A. Serdaroğlu;S. Akpek
455 Remicade在欧洲的销售额从前一年的23亿美元下降到去年的17.9亿美元。在另一份指南草案中，FDA制定了生物仿制药标签的新规则。就在这份新文件发布的一年多前，美国监管机构批准了首个生物相似的Zarxio。但该药物使用的标签受到了制药公司的严厉批评，因此，FDA建议，为避免混淆，生物仿制药的标签通常不应包括证明与其参考产品生物相似的临床试验数据。指南草案还就何时使用生物相似的产品名称(如英夫利昔单抗的“Inflectra”)、仅使用参考产品名称(“Remicade”)或核心产品名称(“英夫利昔单抗”)提出了建议。可互换性问题--在参考产品和生物相似产品之间进行切换--仍有待解决。目前尚不清楚Inflectra将于何时登陆美国市场。总部位于纽约的辉瑞公司将销售这种生物相似药物，该公司表示，正在准备在今年晚些时候推出该药物。强生希望让Inflectra在场边观望一段时间。该公司去年在马萨诸塞州的联邦法院起诉Celltrion，指控Inflectra将侵犯Remicade的六项专利，其中一项专利将于2027年到期。涵盖该药物成分的专利将于2018年到期。Celltrion否认了侵权指控。据伯恩斯坦的Gal称，德国慕尼黑的伊娃·冯·沙珀在美国获得了批准。安进在2005年向FDA提交了一份申请，要求购买总部位于芝加哥北部的AbbVie的Humira(Adalimumab)的副本，这是一种治疗类风湿性关节炎的畅销药物，去年的销售额为140亿美元。Sandoz是总部位于瑞士巴塞尔的诺华公司的子公司，去年10月要求FDA支持仿制安进公司自己的Enbrel(依那西普)，这是一种治疗类风湿性关节炎等自身免疫性疾病的药物，2015年销售额为53亿美元。尽管扬森生物科技公司的母公司强生公司对使用外推法提出了抗议，但该机构还是获得了该机构的认可和随后的监管批准。强生首席生物技术官杰伊·西格尔表示：“我们有很多理由质疑这些药物是否会起到同样的作用。”“我们希望并期待FDA认真对待这些考虑。”强生每年在美国的Remicade销售额约为45亿美元。欧洲药品监管机构2013年批准Celltrion产品的决定也是基于推断。生物相似版本的Remicade已经在多个地区获得批准，包括欧洲部分地区、加拿大、韩国、日本和印度。2014年，加拿大药品监管机构加拿大卫生部批准Celltrion的英夫利昔单抗副本用于除溃疡性结肠炎和克罗恩病(统称为炎症性肠病，或IBD)以外的所有适应症，结论是，由于可能与这些适应症相关的抗体依赖细胞细胞毒性(ADCC)的微小差异的作用和影响的挥之不去的不确定性，不建议将类风湿性关节炎和强直性脊柱炎的设置数据外推到IBD适应症。加拿大卫生部在其决定中辩称，这一立场得到了以下观察的支持，即由总部设在布鲁塞尔的UCB以Cimzia销售的certolizumab pegol缺乏诱导ADCC的能力，对克罗恩病患者只显示出微乎其微的疗效。根据Bernstein‘s Gal的说法，FDA的决定也可能对Inflectra在美国的商业成功产生影响。由于批准只包括部分适应症，它可能已经劝阻了担心质量问题的医生不要开这种药。“反对生物仿制药的最明显的理由是，即使是监管机构也在批准生物仿制药方面存在矛盾，”盖尔说。据Celltrion的Kudrin称，在一些欧洲国家，仿制药基本上已经取代了品牌药物，Celltrion的产品在挪威的市场份额超过90%。今年2月，英国胃肠病学会发布了新的指导意见，建议医疗专业人员认为病情稳定的患者可以改用生物相似的英夫利昔单抗。位于新泽西州凯尼尔沃斯的默克公司
455 Remicade in Europe, saw sales of the drug drop to $1.79 billion last year from $2.3 billion in the previous year. In a separate draft guidance, the FDA set new rules on labeling biosimilars. The new document comes just over a year after the US regulator approved the first biosimilar Zarxio. But the labeling used for the drug was heavily criticized by pharma and, as a result, the FDA recommends that, to avoid confusion, biosimilars’ labels typically should not include clinical trial data demonstrating biosimilarity to their reference products. The draft guidance also makes recommendations of when to use the biosimilar product name (such as ‘Inflectra’ of infliximab-dyyb), just the reference product name (‘Remicade’), or the core product name (‘infliximab’). The issue of interchangeability— switching between the reference product and a biosimilar—remains to be addressed. It isn’t clear when Inflectra will hit the US market. New York–based Pfizer, which will market the biosimilar, has stated that it is preparing the drug’s launch for later this year. J&J is hoping to keep Inflectra on the sidelines for a bit longer. The company sued Celltrion in federal court in Massachusetts last year, alleging that Inflectra would infringe six patents for Remicade, including one that expires in 2027. The patent covering the drug’s composition is due to expire in 2018. Celltrion has denied the infringement allegations. Eva von Schaper Munich, Germany approvals in the US, according to Bernstein’s Gal. Amgen filed in 2005 an application with the FDA for a copy of North Chicago–based AbbVie’s Humira (adalimumab), a best-selling treatment for rheumatoid arthritis that garnered $14 billion in sales last year. Sandoz—a unit of Basel, Switzerland–based Novartis—last October asked the FDA to back a knockoff of Amgen’s own Enbrel (etanercept), a drug to treat autoimmune diseases such as rheumatoid arthritis that had $5.3 billion in sales in 2015. The agency’s endorsement and subsequent regulatory approval came despite the protests of Johnson & Johnson, the parent company to Janssen Biotech, over the use of extrapolation. “We see lots of reasons for questioning whether these drugs will work the same,’’ says Jay Siegel, J&J’s chief biotechnology officer. “We hoped and expected that the FDA take those considerations seriously.’’ J&J has about $4.5 billion in annual US Remicade sales at stake. Europe’s drug regulator also based its 2013 decision to approve the Celltrion product, called Remsima in Europe, on extrapolation. A biosimilar version of Remicade has already been approved in various regions, including parts of Europe, Canada, South Korea, Japan, and India. In 2014, the Canadian drug regulator Health Canada approved Celltrion’s infliximab copy for all indications except ulcerative colitis and Crohn’s disease (collectively referred to as inflammatory bowel disease, or IBD), with the conclusion that extrapolation of data from the settings of rheumatoid arthritis and ankylosing spondylitis to IBD indications could not be recommended owing to lingering uncertainty regarding the role and impact of small differences in antibody-dependent cellular cytotoxicity (ADCC) that might have relevance in these indications. In its decision, Health Canada argued that this position is supported by the observation that certolizumab pegol, marketed by Brusselsbased UCB as Cimzia, which lacks the ability to induce ADCC, displays only marginal efficacy in patients with Crohn’s disease. The FDA’s decision also may have an impact on the US commercial success of Inflectra, according to Bernstein’s Gal. Because the approval includes only a subset of indications, it may have dissuaded doctors worried about quality from prescribing the drug. “The most obvious argument against biosimilars would be that even regulators are conflicted about approving biosimilars,’’ says Gal. In some European countries, the copy has essentially displaced the branded drug, with the market share of Celltrion’s product at over 90% in Norway, according to Celltrion’s Kudrin. In February, the British Society of Gastroenterology released new guidance advising that patients whose condition is considered by medical professionals to be stable can be switched to biosimilar infliximab. Merck, of Kenilworth, New Jersey, which markets