FDA顾问委员会建议批准强生丙肝新药simeprevir

强生（JNJ）10月24日宣布，FDA抗病毒药物顾问委员会（ADAC）一致投票（19:0），建议批准实验性蛋白酶抑制剂simeprevir（TMC435），联合聚乙二醇干扰素和利巴韦林（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。

FDA审查员于10月22日发布了积极意见，认为simeprevir在临床试验中表现出了可接受的安全性。此外，FDA于今年5月授予simeprevir新药申请（NDA）优先审查资格。

Simeprevir监管文件的提交，部分由3个关键性III期临床试验数据支持：QUEST-1和QUEST-2在初治患者中开展，PROMISE则在基于干扰素疗法治疗后复发的患者中开展。

最近，扬森也已向日本和欧洲的监管机构提交了simeprevir的监管申请文件。

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。在美国，约有320万丙型肝炎患者，每年约有1.5万人死于该病，大多死于丙型肝炎相关疾病，如肝硬化和肝癌。

关于simeprevir：

Simeprevir是新一代NS3/4A蛋白酶抑制剂，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。

今年9月，simeprevir（商品名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。

Sovriad为每日一次的口服胶囊，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：sovriad+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。

英文原文：FDA Advisory Committee Recommends Approval of Simeprevir for Combination Treatment of Genotype 1 Chronic Hepatitis C in Adult Patients
RARITAN, N.J. (October 24, 2013) -- Janssen Research & Development, LLC (Janssen) announced today that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) voted unanimously (19 to 0) to recommend approval of the investigational protease inhibitor simeprevir (TMC435) administered once daily as a 150 mg capsule with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis. The Advisory Committee recommended the approval of simeprevir based on analyses of data from clinical trials in patients who are treatment naïve or who have failed previous interferon-based therapy.

“We are pleased with the positive recommendation from the Advisory Committee for simeprevir and appreciate the rigorous review of our data,” said Katia Boven, M.D., Medical Department Head, Infectious Diseases and Vaccines, Janssen. “It is our hope that the FDA will consider this recommendation and, upon completion of its review process, make simeprevir available to patients with genotype 1 chronic hepatitis C.”

The FDA granted a Priority Review designation in May to the New Drug Application (NDA) filed by Janssen for simeprevir. Recommendations and findings from the Advisory Committee are based in part on efficacy and safety data from an extensive clinical development program for simeprevir and will be considered by the FDA in its review of the NDA for simeprevir, but the FDA is not required to follow them. 

The regulatory submission for simeprevir is supported in part by data from three pivotal Phase 3 studies – QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients. Janssen R&D Ireland presented data from the QUEST-1 and QUEST-2 studies earlier this year at the 48th Annual Meeting of the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands, and presented data from PROMISE at Digestive Disease Week 2013 (DDW) in Orlando, Florida. Data from ASPIRE were presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in 2012.

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide – including approximately 3.2 million people in the United States – and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 and genotype 4 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for simeprevir in Nordic countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C and a Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.