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丙肝特效药:搞不懂的吉利德

已有 14963 次阅读 2014-9-26 07:25 |个人分类:肝病手记|系统分类:海外观察| 丙型肝炎, 抗病毒药物, 吉利德

  吉利德科學公司(Gilead Sciences,Inc.,NASDAQ:GILD)是位於美國加利福尼亞州的一家1987年成立的獨立的生化公司。該公司所開發和銷售的藥物廣泛應用于病毒、真菌和細菌感染,公司擁有liposomal藥物專門對付技術,該技術的利用使藥物對患者更加安全、簡單和有效。美國國防部長拉姆斯菲爾德於1997至2001年間,為吉利德的董事會主席。

  治疗慢性丙型肝炎的特效药物Sovaldi是“吉利德”名副其实的印钞机,2014上半年的销售额达到了惊人的58亿美元。Sovaldi于2013年12月在美国上市,自诞生之日便成为行业关注的焦点,其84000美元/疗程(1000美元/片)的定价也饱受各方争议。美国众议院、患者维权组织等机构曾强烈呼吁Sovaldi降价,而“吉利德”则坚持不降,他们宣称从长远来看,该药将为纳税人节省大笔开支。

  在美国,约有300-400万丙肝患者。在Sovaldi上市之前,丙肝的临床标准治疗需要每日服用多达12片药物,同时必须注射干扰素,该标准疗法的临床治愈率仅为75%左右,并可引起类似流感症状的严重副作用。而Sovaldi的副作用少,且治愈率高达80%-90%,因此一上市便迅速获得了临床医生的青睐。

  但是,“吉利德”最近宣布,已经与多家仿制药商达成合作协议,生产丙肝明星药物Sovaldi的仿制药及另一种实验性药物,销往91个北非、中亚和东亚的发展中国家,然而,中国却并未被包含在内。

  今年8月,“吉利德”接受《印度时报》采访时表示,将在印度以1%的价格销售Sovaldi,即900美元/疗程,折扣高达99%,遭到了美国评论家的强烈声讨。但吉利德表示,该定价是基于面对低收入国家的定价策略。“吉利德”表示,协议所覆盖的国家中,丙肝患者总数超过1亿例,超过了全球丙肝患者总数的一半。此次与仿制药商达成的协议,对于吉利德在这些发展中国家人道主义项目的推进至关重要。

  此次合作名单中有7家印度仿制药公司,其中包括迈兰(Mylan)、兰伯西(Ranbaxy)和Cadila保健公司。迈兰称,该笔交易将允许旗下子公司生产Sovaldi的仿制药,并将帮助解决数以百万计患者的医疗需求。这些公司将向吉利德支付基于销售额的特许权使用费,同时吉利德将转让Sovaldi生产技术,以帮助其迅速开始生产。

  此次合作的协议,还包括吉利德另一种丙肝复方药物,该药由Sovaldi和另一种抗病毒药物ledipasvir组成,目前该复方药正在接受FDA和欧洲药品管理局(EMA)的审查。

   吉利德”执行副总裁Gregg Alton在一份声明中称:公司在谈判时,会根据一个国家的人均收入和丙型肝炎的发病率,分为有3种定价策略:低收入、中等收入和高收入。根据世界卫生组织(WHO),印度有1200万慢性丙型肝炎(HCV)患者;而根据世界银行,2009-2013年,印度的人均收入仅为1499美元,相比之下,美国的人均收入为53143美元。

    尽管如此,看到“吉利德”对采取1%的巨大价格差异来销售Sovaldi,仍然让人感到有些不可思议。按说,即使采取10%-20%的价格差异销售仿制药品,也是对发展中国家相当不错的人道主义援助,而且可以减少本国民众以及其他国家的极大不满(难怪美国民众大为恼火,敢情印度人民才是吉利德的亲爹亲娘呐),难道美国人做事就是要如此独行特立?当然,也有业界认为“吉利德”此举,更多的或是出于对印度知识产权大环境的无奈之举。如果印度政府行使强制仿制许可权,吉利德不仅丧失了在印度的直接销售,甚至有失去Sovaldi专利的风险。

    据说,根据世界贸易组织相关协议,成员国发生公共健康危机,如艾滋病、疟疾、肺结核和其他流行疾病时,可考虑实施药品专利强制许可,仿制生产仍在专利期限内的药物来解决公众危机。巴西、南非、泰国等国就曾对治疗艾滋病等传染病的二线药物实施过强制许可。而在2012年3月,印度政府批出了有史以来的第一个抗癌药物的强制许可,允许本土制药商生产德国制药商拜耳(Bayer)公司抗癌药物Nexavar的仿制版药物,这一强制许可,允许印度的Natco制药将每月剂量以8800卢比(约160美元)的价格销售Nexavar仿制药,与拜耳公司的原药相比降价幅度达到97%。

  这条强制许可的出现,使外国制药公司对新兴市场药物知识产权保护的缺乏产生了担忧,同时也改变了在新兴市场的销售策略以减少自身损失。因此,吉列德公司为了防止印度再次以强硬手段生产仿制药影响自身利益,特别允许印度等91国在协议范围内制造和销售仿制药。
  而在中国,自2012年5月1日国家知识产权局更新《专利实施强制许可办法》施行至今,虽然中国民间对乙肝、艾滋病等相关治疗药物申请强制许可的呼声不断,但无一款药物获得国家批准。这是政府的保守还是政策的疲软?
 

  附:Gilead Sciences

  Gilead SciencesNASDAQ: GILD is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two companies that were developing drugs to treat patients with pulmonary diseases. The company has eleven commercially available products. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia. As of Jan. 31, 2008, the company had 2,979 full-time employees.

  The company's name and logo refer to the Balm of Gilead. Gilead (a place mentioned in the Bible) was famed for its small trees that produced a resin (similar to frankincense and myrrh) used in medicine is considered to be the “first genuine pharmaceutical product.” The leaf in the logo symbolizes healing, life and growth, while the shield represents safety, strength and honor. Together they signify Gilead's efforts to use the healing power of science to create medicines that treat life-threatening diseases.

  Gilead is a member of the NASDAQ Biotechnology Index and theS&P 500.

  History

  Gilead Sciences was originally formed under the name of “Oligogen, Inc.” in August 1987 by Michael Riordan, a medical doctor who was 29 years old at the time. The name of the company was changed to "Gilead Sciences" in 1988. Riordan looked to Donald Rumsfeld as a mentor in the business world and to navigate the political waters. Under the technicalleadershipof scientist Mark Matteucci, the company focussed on discovery research, making small strands of DNA (oligomers) to assess the potential of genetic code blockers (gene therapy). Its development of small molecule antiviral therapeutics was ushered in by John Martin in 1992 with the licensing of nucleotide compounds discovered in two European academic labs.

  In 1990, Gilead entered into a collaborative research agreement with Glaxo for the research and development of genetic code blockers, also known as antisense. This collaboration was terminated in 1998, and Gilead's antisense intellectual property portfolio was sold to Isis Pharmaceuticals.

  Gilead debuted on the NASDAQ in January 1992. Its IPO raised $86.25 million in proceeds.

  In June 1996, Gilead launched its first commercial product, Vistide (cidofovir injection) for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. The company cooperated with Pharmacia & Upjohn to market the product outside the U.S.A.

  In March 1999 Gilead acquired NeXstar Pharmaceuticals of Boulder, Colorado following two years of negotiations with the company. At the time, NeXstar's annual sales of $130 million was three times Gilead's sales. NeXstar's two revenue-generating drugs were AmBisome, an injectable fungal treatment, and DaunoXome, an oncology drug taken by HIV patients. Also in 1999, Roche announced first approval of Tamiflu (oseltamivir) for the treatment of influenza. Tamiflu was originally discovered by Gilead and licensed to Roche for late-phase development and marketing.

  Viread (tenofovir) achieved first approval in 2001 for the treatment of HIV.

  In January 2003 Gilead completed its acquisition of Triangle Pharmaceuticals. The company also announced its first full year of profitability. Later that year Hepsera (adefovir) was approved for the treatment of chronic hepatitis B, and Emtriva (emtricitabine) for the treatment of HIV.

  In 2004 Gilead launched Truvada, a fixed-dose combination of tenofovir and emtricitabine.

  In January 1997, Donald Rumsfeld, a Board member since 1988, was appointed Chairman of the company. He stood down from the Board in January 2001 when appointed Secretary of Defense at the start of George W. Bush's first term as President. Federal disclosure forms indicate that Rumsfeld owns betweenUSD$5 million and USD$25 million in Gilead stock. The rise in Gilead's share prices from USD$35 to USD$57 per share will have added between USD$2.5 million to USD$15.5 million to Rumsfeld's net worth.

  In November 2005, George W. Bush urged Congress to pass $7.1 billion in emergency funding to prepare for the possible bird flu pandemic, of which one billion is solely dedicated to the purchase, and distribution of Tamiflu.

  In July 2006, the U.S.Food and Drug Administration (FDA) approved Atripla, a once a day single tablet regimen for HIV, combining Sustiva (efavirenz), aBristol-Myers Squibbproduct, and Truvada (emtricitabine and tenofovir disoproxil fumarate), a Gilead product.

  Gilead purchased Raylo Chemicals, Inc. in November 2006 for a price of $133.3 million. Raylo Chemical, based in Edmonton, Alberta, was a wholly-owned subsidiary of Degussa AG, a German company. Raylo Chemical was a custom manufacturer of active pharmaceutical ingredients and advanced intermediates for the pharmaceutical and biopharmaceutical industries.



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