OLYSIO™ (simeprevir) was approved by the U.S. Food and Drug Administration (FDA) on November 22nd, 2013 for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis.

The treatment was approved in September 2013 in Japan under the trade name SOVRIAD™ and in November 2013 in Canada under the trade name GALEXOS™ for the treatment of genotype 1 hepatitis C.

OLYSIO™ (simeprevir), an NS3/4A protease inhibitor administered as one capsule once daily, was developed by Medivir and Johnson & Johnson’s pharmaceutical division Janssen Pharmaceutical. Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That’s roughly $66,360 for a three-month course.

The previous standard of care for hepatitis C was a year-long regimen of pills and injections. The injections consist of an immune-boosting drug called Peginterferon (pegylated interferon), which often causes intolerable side effects. The pills included the nucleoside inhibitor ribavirin plus either Merck’s Victrelis (boceprevir) or Vertex’s Incivek (telaprevir) —first-generation regimens that produced cure rates between 65% and 75%. When Olysio is used with interferon and ribavirin, the combination “cured 80% of patients who had not previously been treated for the disease,” according to an FDA advisory report.

Simeprevir is the third hepatitis C protease inhibitor on the US market after Merck & Co’s Victrelis (boceprevir) and J&J/Vertex Pharma’s Incivek (telaprevir), which were approved in 2011. Sales of Victrelis and Incivek have started to stall this year as a host of better agents coming through development, That trend makes it hard to predict the prospects for simeprevir, ahead of all-oral regimens that are due to become available in 2014.  J&J claims that simeprevir is the most potent compound in its class. Analysts have suggested sales could reach $400m or more within two years.

Simeprevir and telaprevir are used for 12 weeks while boceprevir is used from 24 to 44 weeks. Simeprevir is taken once daily, with food. Boceprevir and telaprevir are oral drugs that need to be taken three times a day with a meal or snack.

The FDA is slated to decide by December 8 on Gilead Sciences’ application for its NS5B polymerase inhibitor Sovaldi (sofosbuvir), which could become the first all-oral treatment for two less common forms of hepatitis C (genotypes 2 and 3) in combination with ribavirin.  Analysts have predicted that sofosbuvir could become a mega blockbuster with sales of $5bn a year or more at peak.. Gilead got sofosbuvir in its $11 billion buyout of Pharmasset in 2011. (Update: Sovaldi(sofosbuvir) was approved by U.S. FDA on December 6, 2013).

Other companies working to develop new hepatitis C drugs include AbbVie and Bristol-Myers Squibb.

AbbVie, the pharmaceuticals business spun off by Abbott Laboratories early this year, reported this month  a 631-patient Phase III SAPPHIRE-I study (M11-646) of its experimental oral hepatitis C “3D” regimen (ABT-450/r + ABT-267 + ABT-333) showed about 96 percent of patients had no detectable levels of the virus after 12 weeks. Patients new to therapy receiving 12 weeks of AbbVie’s ritonavir-boosted HCV protease inhibitor ABT-450 plus the NS5A inhibitor ABT-267 in a fixed-dose combination pill, taken along with the non-nucleoside polymerase inhibitor ABT-333 and ribavirin. achieved a sustained virologic response at 12 weeks post-treatment (SVR12) of 96 percent. The company plans to submit data for regulatory approval in the second quarter of 2014.

Bristol-Myers Squibb received “breakthrough” status from FDA early this year for a combination of daclatasvir (BMS-650032) with two other direct-acting antivirals, asunaprevir (BMS-650032), an NS3 protease inhibitor and BMS-791325, an NS5B non-nucleoside polymerase inhibitor.

Brand name: Olysio (US), Sovriad(Japan), Galexos(Canada)
Generic name: simeprevir
Synonyms: TMC-435; TMC435350
CAS Number:923604-59-5
Approval Date:November 22nd, 2013 (US), September 2013 (Japan)
Indication: Genotype 1 chronic hepatitis C
Mechanism of Action:HCV NS3/4A protease inhibitor
Cost:$790 per pill;$22,120 per bottle of 28 capsules (150 mg capsules);$66,360 for a three-month course
Company:Johnson & Johnson, Medivir
Patents:US8148399,US8153800,US8349869,US7608590,US7671032,
Patent Expiration Date:Jan 2026 for US 8148399,US 8153800 and US 8349869;Jan 2025 for US7608590 and US7671032

强生旗下丙型肝炎药物Olysio(Simeprevir)获FDA批准

2013年11月22日，美国食品药品管理局（FDA）批准新型治疗药物Olysio(Simeprevir)联合聚乙二醇干扰素(Peginterferon)和利巴韦林（ribavirin），用于基因型1慢性丙型肝炎成人患者代偿性肝脏疾病（包括肝硬化）的治疗.

今年9月，simeprevir（在日本的商品名为Sovriad）获日本劳动卫生福利部（MHLW）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，这是simeprevir获得的全球首个监管批准。

Simeprevir由Medivir公司和杨森（Janssen）联合开发，其工作原理是通过阻断NS3/4A蛋白酶，来抑制HCV在肝脏细胞中的复制。 simeprevir是每日一次的口服药物，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是FDA批准的第三款治疗慢性丙型肝炎病毒（HCV）感染的NS3/4A蛋白酶抑制剂, 2011年，FDA批准默沙东的博赛匹韦(波普瑞韦, 博赛泼维, Boceprevir，Victrelis)和Vertex制药公司的特拉匹韦(特拉泼维, Telaprevir，Incivek)用于丙型肝炎治疗。波西普韦与特拉普韦均在丙型肝炎领域产生了巨大的影响，提高了以干扰素为基础治疗方案的有效性，并快速进入市场，2012年两款药物的销售额分别为5.02亿美元和12亿美元。但波西普韦与特拉普韦今年的销售开始停滞，在2014年全口服治疗方案可供使用之前，这种销售下滑趋势使得预测Simeprevir的前景变得非常困难。强生称Simeprevir是这类药物中最有效的药物。分析师认为这款药物在两年内的销售额可能会达到4亿美元或更多。

蛋白酶抑制剂类药物涌现出的其它药物包括勃林格殷格翰的Faldaprevir，默沙东的Vaniprevir，百时美施贵宝的Asunaprevir，以及艾伯維(Abbvie)的ABT 450，这类药物据称与第一代药物相比有优越的病毒治愈率和更温和的副作用。

吉利德科学公司（Gilead)于2013年4月提交了丙肝重磅炸弹sofosbuvir的新药申请（NDA），FDA于2013年6月授予sofosbuvir优先审查资格。FDA审查员10月23日称，吉利德（Gilead）开发的NS5B聚合酶抑制剂sofosbuvir在与其他疗法联合用于丙型肝炎（hepatitis C）治疗时安全有效。10月25日，FDA抗病毒药物顾问委员会（ADAC）一致投票（15:0）支持批准实验性核苷类似物sofosbuvir联合利巴韦林（ribavirin）用于基因型2和基因型3慢性丙肝（hepatitis C）成人患者的治疗。FDA将于2013年12月8日前做出最后决定。分析师已预测Sofosbuvir可能会成为一款超级重磅炸弹级产品，其销售峰值会达到50亿美元。

艾伯维公司(Abbvie)2013年11月刚公布了其复方药物(ABT-450/r+ABT-267+ABT-333)第一个III临床试验M11-646(SAPPHIRE-I)（共有6个III临床试验）的最新结果.三联全部口服的三联组合药物由ABT-450/r(NS3/4A蛋白酶抑制剂和低剂量利托那韦ritonavir)、ABT-267(NS5A抑制剂)和ABT-333(非核苷聚合酶抑制剂)组成。对于既往未接受治疗的HCV GT1感染患者，在不含聚乙二醇干扰素α的情况下，三联全部口服的组合(ABT-450/r+ABT-267+ABT-333）+利巴韦林组（n=631）应答率达到了96%。而simeprevir+聚乙二醇干扰素α+利巴韦林组应答率只有75%. 艾伯维公司(Abbvie)的全口服三联疗法2013年5月6日曾被FDA授予突破性药物资格，艾伯维计划在2014年第二季度提交NDA申请。

商品名：Olysio （美国）,Sovriad( 日本), Galexos(加拿大)
通用名：simeprevir
中文名:暂无
别名:TMC-435; TMC435350
CAS 登录号:923604-59-5
批准时间:2013年11月22日(美国),2013年9月(日本)
适应症:慢性丙型肝炎(HCV GT1)
作用原理：NS3/4A蛋白酶抑制剂
费用：每粒胶囊790美元
生产商:强生,Medivir
美国专利号：US8148399,US8153800,US8349869,US7608590,US7671032
专利到期时间：2026年1月（US8148399,US8153800,US8349869）;2025年1月（US7608590,US7671032）