吉利德丙肝新药Sovaldi获FDA批准

吉利德（Gilead）12月6日宣布，丙肝新药Sovaldi（sofosbuvir，400mg片剂）获FDA批准，作为抗病毒治疗方案的一部分，用于慢性丙型肝炎（HCV）的治疗。Sovaldi是首个获批可用于C型肝炎全口服治疗方案的药物，在用于特定基因型慢性丙型肝炎治疗时，可消除对传统注射药物干扰素（IFN）的需求。

具体而言，FDA已批准sofosbuvir联合利巴韦林（ribavirin）用于基因型2和基因型3慢性丙型肝炎（hepatitis C）成人患者的治疗。同时，FDA还批准sofosbuvir联合聚乙二醇干扰素（PEG-IFN）和利巴韦林，用于基因型1和基因型4慢性丙型肝炎初治（treat-naive）成人患者的治疗。

Sofosbuvir为每日一次的口服核苷类似物聚合酶抑制剂。吉利德于2013年4月提交了sofosbuvir的新药申请（NDA），此前FDA已授予sofosbuvir优先审查资格及突破性疗法认定。

目前，在美国，约有400万慢性丙型肝炎患者，其中大部分出生于1945年-1965年婴儿潮时期。慢性丙型肝炎是导致肝癌和肝移植的首要原因，在最近几年来，作为致死病因，HCV已超过了HIV/AIDS。当前，HCV的标准护理包括48周的含聚乙二醇化干扰素（PEG-IFN）/利巴韦林（RBV）方案，但这些方案并不总是有效，而且具有显著的副作用，并与其他药物具有用药禁忌。

Sovaldi的获批，主要基于4个III期研究（NEUTRINO, FISSION, POSITRON, FUSION）的数据。在FDA审查期间，2个新的III期研究（VALENCE和PHOTON-1）添加至sofosbuvir的新药申请（NDA），FDA根据这些数据，授予sofosbuvir突破性疗法认定。

根据汤姆森路透的数据，分析师们平均预测，sofosbuvir在2014年的销售额将达到19亿美元。Gilead则估计，sofosbuvir一旦上市，市值将达110亿美元。

根据吉利德，在美国，28片/瓶装Sovaldi的批发商采购成本（WAC）费用将为2.8万美元，即每片1000美元，大多数患者需要治疗12周，总费用将达8.4万美元。

英文原文：U.S. Food and Drug Administration Approves Gilead’s Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C

– Sovaldi Approved for Use in Genotypes 1, 2, 3 or 4 –

– High Cure Rates (SVR12) and Shortened, 12-Week Course of Therapy for Many Patients –

– First Ever Oral Treatment Regimen for Genotypes 2 or 3 –

– First Regimen for Patients Awaiting Liver Transplantation to Prevent HCV Recurrence –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Dec. 6, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Sovaldi™ (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. Sovaldi’s efficacy has been established in subjects with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Recommended regimens and treatment duration for Sovaldi combination therapy in HCV mono-infected or HCV/HIV-1 co-infected patients follows.
                 
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended. Full Prescribing Information will be available on www.Gilead.com.

The FDA granted Sovaldi Priority Review and Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.

“I believe that Sovaldi will have a major impact on public health by significantly increasing the number of Americans who are cured of hepatitis C,” said Ira Jacobson, MD, Chief of the Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City and a principal investigator in the Sovaldi clinical trials. “In clinical studies, Sovaldi in combination with other agents achieved very high cure rates while shortening the duration of treatment to as little as 12 weeks and reducing or completely eliminating the need for interferon injections, depending on the viral genotype.”

Chronic hepatitis C affects an estimated 4 million people in the United States, the majority of whom are “baby boomers” – individuals born between 1945 and 1965. The disease is the nation’s leading cause of liver cancer and liver transplantation, and in recent years has surpassed HIV/AIDS as a cause of death. The current standard of care for HCV involves up to 48 weeks of therapy with a pegylated interferon (peg-IFN)/ribavirin (RBV)-containing regimen, which may not suitable for certain types of patients.

“It is our hope that Sovaldi will mark the beginning of a new era in hepatitis C treatment. Gilead is proud to have played a role in bringing about this important therapeutic advance and we would like to extend our thanks to the many patients and physicians who partnered with us on Sovaldi’s clinical studies,” said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences.

Sovaldi’s approval is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, which evaluated 12 or 16 weeks of treatment with Sovaldi combined with either RBV or RBV plus peg-IFN. Three of these studies evaluated Sovaldi plus RBV in genotype 2 or 3 patients who were either treatment-naïve (FISSION), treatment-experienced (FUSION) or peg-IFN intolerant, ineligible or unwilling (POSITRON). NEUTRINO evaluated Sovaldi in combination with Peg-IFN/RBV in treatment naïve patients with genotypes 1, 4, 5 or 6. In these studies, Sovaldi-based therapy was found to be superior to historical controls (NEUTRINO and FUSION) or to placebo (POSITRON), or non-inferior to currently available treatment options (FISSION) based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. Trial participants taking Sovaldi-based therapy achieved SVR12 rates of 50-90 percent. For full study details, see the Clinical Studies section of the full Prescribing Information.

During the FDA’s review, data from two additional Phase 3 studies, VALENCE and PHOTON-1, were added to the NDA as a result of the Breakthrough Designation status. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. Eighty-four percent of patients in this trial achieved SVR12. The PHOTON-1 study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. Trial participants achieved SVR12 rates of 76-92 percent. In all Phase 3 studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.

To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase 2 or 3 studies. Sovaldi combination therapy was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events. The most common adverse events occurring in at least 20 percent of patients receiving Sovaldi in combination with Peg-IFN/RBV were fatigue, headache, nausea, insomnia and anemia; see below for Important Safety Information regarding contraindications, warnings and precautions, adverse reactions and drug interactions.

On November 22, 2013, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion on Gilead’s application for marketing authorization for Sovaldi. The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. This assessment does not guarantee marketing authorization by the European Commission. If approved, Sovaldi could be available in the European Union in the first quarter of 2014. Applications for marketing approval of Sovaldi are also pending in Australia, Canada, New Zealand, Switzerland and Turkey.

Dr. Jacobson is a paid consultant to Gilead.

The Wholesaler Acquisition Cost (WAC) of a 28-tablet bottle of Sovaldi in the United States is $28,000.