Harvoni

Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively...

Treatment for chronic hepatitis C depends on the hepatitis C virus (HCV) genotype and the patient's clinical characteristics. A fixed-dose combination of ledipasvir + sofosbuvir has been authorised in the European Union for adults with HCV genotype 1 (HCV-1), HCV-3 or HCV-4 infection. Ledipasvir targets the HCV protein NS5A, while sofosbuvir inhibits the HCV RNA polymerase NS5B. The ledipasvir+ sofosbuvircombination has not been compared directly with other antiviral drugs. No information is available on its ability to prevent hepatic complications, even in patients with cirrhosis...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of Sovaldi™, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977...

Chronic hepatitis C (CHC) affects over 185 million individuals worldwide, approximately 3% of the world's population. CHC can lead to quality of life impairment, cirrhosis, hepatocellular carcinoma (HCC), liver failure and liver-related death. While CHC has been associated with increases in HCC, liver-related mortality and all-cause mortality, being cured of CHC is associated with improvement in these outcomes. Older interferon-based regimens were complex and toxic and required 6-12 months of therapy, with cure rates averaging around 40-45% for HCV genotype 1...

BACKGROUND: New treatments for hepatitis C (HCV) infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications. MATERIALS AND METHODS: We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED) from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times...

BACKGROUND: The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost...

More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response...

The availability of direct-acting antiviral (DAA) therapy has launched a new era in the management of chronic hepatitis C. Sofosbuvir, a uridine nucleotide analog that inhibits the hepatitis C RNA-dependent RNA polymerase, is the backbone of chronic hepatitis C therapy. Acting at the catalytic site of the polymerase, sofosbuvir is highly potent in suppressing viral replication and has a high genetic barrier to resistance. Sofosbuvir is effective across all hepatitis C genotypes, and is a mainstay of interferon-free combination therapy...

The long awaited all-oral therapy for hepatitis C virus infection has officially been inaugurated by the registration of the hepatitis C nucleotide inhibitor sofosbuvir in a combination regimen with ribavirin. More recently, the oral array to treat hepatitis C has been enriched by the arrival of the NS5A inhibitors ledipasvir (also in a single formulation with sofosbuvir, Harvoni(®)) and daclatasvir; the protease inhibitor simeprevir, and the Viekirax(®)+Exviera™ regimen based on the ritonavir boosted protease inhibitor paritaprevir; the NS5A inhibitor ombitasvir, and the non-nucleoside inhibitor dasabuvir...

Hepatitis C infection can cause chronic liver disease and liver carcinoma and can necessitate liver transplantation. Of the more than 3 million people infected with hepatitis C, more than two-thirds were born between 1945 and 1965. Many individuals are unaware that they're infected, which can delay treatment and lead to disease progression. Once infection is diagnosed, typical treatment regimens can involve multiple medications and side effects that can make it challenging for some people to complete therapy...

Ledipasvir/sofosbuvir (Harvoni): improving options for hepatitis C virus infection.

PURPOSE: Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regarding the benefits of Sovaldi® relative to its costs. METHODS: A comprehensive review was conducted of news stories highlighted in the daily updates of the electronic newsletters BIO SmartBrief, FiercePharma, FierceBiotech and BioCentury Extra published from November 1, 2013, through December 31, 2014, on the topics of the HCV market, Sovaldi®, and other HCV therapeutics...

The single-tablet regimen of the hepatitis C virus (HCV) NS5A inhibitor ledipasvir and the HCV NS5B polymerase inhibitor sofosbuvir (ledipasvir/sofosbuvir; Harvoni(®)) was recently approved in the US and the EU. The phase III ION trials included treatment-naive (ION-1 and -3) or treatment-experienced (ION-2) patients with chronic HCV genotype 1 infection (≈20 % of patients in ION-1 and -2 had cirrhosis, whereas no patient in ION-3 had cirrhosis). A sustained virological response 12 weeks' post-treatment (SVR12) was seen in 99 % of treatment-naive patients receiving ledipasvir/sofosbuvir for 12 weeks in ION-1, with no additional benefit conferred by the addition of ribavirin or extending the treatment duration to 24 weeks...

BACKGROUND: New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown. METHODS: We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective...

Ledipasvir/sofosbuvir (Harvoni) for hepatitis C virus genotype 1 infection; dulaglutide (Trulicity) for glycemic control in type-2 diabetes; netupitant/palonosetron (Akynzeo) for prevention of nausea and vomiting related to chemotherapy; and naloxegol (Movantik) for opioid-induced constipation in patients with chronic noncancer pain.

No abstract text is available yet for this article.