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Givinostat (DUVYZAT™), an orally available histone deacetylase inhibitor, is being developed by Italfarmaco for the treatment of muscular dystrophy and polycythemia vera. Givinostat received its first approval on 21 March 2024, in the USA, for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older. Approval was based on the results of the multinational phase III EPIDYS trial, in which givinostat recipients showed less decline than placebo recipients in the time taken to perform a functional task. Givinostat represents the first nonsteroidal treatment for DMD to be approved for use in patients irrespective of the specific genetic variant underlying their disease. Givinostat is available as an oral suspension to be administered twice daily with food. The recommended dosage is based on the body weight of the patient. In the EU, regulatory review of givinostat in DMD is currently underway. This article summarizes the milestones in the development of givinostat leading to this first approval for DMD.

In two trials involving patients with hepatitis C in whom previous treatment with direct-acting antiviral agents failed, treatment for 12 weeks with sofosbuvir, velpatasvir, and voxilaprevir achieved high rates of sustained virologic response. The majority of patients who are chronically infected with hepatitis C virus (HCV) can now be successfully treated with drugs that directly target viral replication. 1 , 2 Combination regimens of direct-acting antiviral agents (DAAs) provide rates of sustained virologic response exceeding 90%, regardless of HCV genotype, disease stage, or treatment history. 3 The proportion of patients who do not have a sustained virologic response to treatment with approved regimens is small, but given the size of the infected population — estimates range up to 150 million people worldwide 4 — the absolute number of such patients is substantial and will increase as more . . .

In two phase 3 trials involving patients with hepatitis C virus infection, including those with cirrhosis, 12 weeks of sofosbuvir–velpatasvir resulted in a sustained virologic response in 99% of patients with genotype 2 and 95% of those with genotype 3. Hepatitis C virus (HCV) genotypes 2 and 3 account for an estimated 35% of global HCV infections, affecting up to 58 million persons. 1 , 2 Unlike HCV genotype 1, genotypes 2 and 3 are common in low-income regions in Asia, sub-Saharan Africa, Latin America, and Eastern Europe. 1 Before the advent of direct-acting antiviral agents, HCV genotypes 2 and 3 were grouped together in treatment guidelines as “easy-to-treat” genotypes. However, recent studies have shown that HCV genotype 3 is associated with more rapid disease progression and lower rates of response to treatment than is HCV genotype 2, especially in patients with cirrhosis . . .

In this phase 3 study involving patients with HCV genotype 1, 2, 3, 4, or 6 and decompensated cirrhosis, sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 weeks resulted in high rates of sustained virologic response. The number of patients with decompensated cirrhosis caused by chronic infection with the hepatitis C virus (HCV) is projected to rise in the coming decade. 1 For many years, the only treatment option for such patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis and that successful treatment is associated with early improvement in liver function. 2 – 11 The possible long-term benefits of treatment on existing liver disease remain unknown. The only regimen that is currently approved for the . . .

In this analysis of the ASTRAL trials (non-opioid substitution therapy [OST], n = 984; OST, n = 51) evaluating the once-daily, pan-genotypic regimen of sofosbuvir/velpatasvir for hepatitis C virus infection, OST did not impact completion, adherence, sustained virologic response (SVR12), or safety. SVR12 was 96% (95% confidence interval, 87%, >99%) in those receiving OST.

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality 1 , 2 , 3 . Current interferon-based therapies 4 are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics 5 , 6 . The HCV-encoded NS3 protease is essential for viral replication 7 , 8 and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.

First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P<0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall survival are now available. We randomly assigned patients with untreated V600E-mutated metastatic colorectal cancer to receive EC, EC+mFOLFOX6, or standard care. The two primary end points were objective response (reported previously) and progression-free survival according to blinded independent central review in the EC+mFOLFOX6 group and the standard-care group. The key secondary end point was overall survival. Significantly longer progression-free survival was seen with EC+mFOLFOX6 than with standard care (median, 12.8 vs. 7.1 months; hazard ratio for progression or death, 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001). In an interim analysis, overall survival was significantly longer with EC+mFOLFOX6 than with standard care (median, 30.3 vs. 15.1 months; hazard ratio for death, 0.49; 95% CI, 0.38 to 0.63; P<0.001). The incidence of serious adverse events during treatment was 46.1% with EC+mFOLFOX6 and 38.9% with standard care. Safety profiles were consistent with those known for each agent. This trial showed significantly longer progression-free survival and overall survival with first-line treatment with EC+mFOLFOX6 than with standard care among patients with V600E-mutated metastatic colorectal cancer. (Funded by Pfizer and others; BREAKWATER ClinicalTrials.gov number, NCT04607421.).

In patients with HCV genotype 1 infection and cirrhosis, the rate of sustained virologic response was 92% with three new antiviral agents plus ribavirin for 12 weeks and 96% with the same regimen for 24 weeks. Two percent of patients discontinued treatment because of adverse events. An estimated 184 million people worldwide have hepatitis C virus (HCV) infection, 1 a leading cause of chronic liver disease and the leading indication for liver transplantation globally. 2 , 3 Approximately 25% of persons with HCV infection in the United States have cirrhosis, and this number is expected to rise to 37% by 2020. 4 , 5 Eradication of HCV with antiviral therapy reduces the risk of hepatic decompensation, hepatocellular carcinoma, and death from a liver-related cause or any cause. 6 – 10 Among patients with HCV infection and cirrhosis in whom peginterferon–ribavirin treatment has failed, rates of sustained virologic response to retreatment with interferon-containing regimens . . .

In this trial in previously untreated patients with HCV genotype 1 infection and no cirrhosis, high rates of sustained response were achieved with three new direct-acting antiviral agents and ribavirin. Serious adverse events and treatment discontinuation were infrequent. Approximately 184 million people worldwide have chronic hepatitis C virus (HCV) infection, and more than 350,000 people die of HCV-related liver disease each year. 1 , 2 Until recently, the standard of care for chronic HCV genotype 1 infection was a first-generation protease inhibitor, telaprevir or boceprevir, with peginterferon and ribavirin; this therapy resulted in rates of sustained virologic response of 67 to 75% among previously untreated patients. 3 , 4 The new standard of care is peginterferon and ribavirin combined with either the nucleotide nonstructural (NS) 5B polymerase inhibitor sofosbuvir or the protease inhibitor simeprevir. 5 Peginterferon-based treatment is associated with clinically significant systemic . . .

Among previously untreated patients with HCV genotype 1 infection, three new antiviral agents, with or without ribavirin, resulted in high rates of sustained virologic response. Omission of ribavirin resulted in reduced response in genotype 1a infection but not in genotype 1b infection. Hepatitis C virus (HCV) infection is a worldwide health issue, with 3 million to 4 million new infections yearly and infection rates as high as 5% in some countries. 1 Chronic infection leads to liver disease, cirrhosis, or liver cancer in a large proportion of infected persons, and hepatitis C accounts for 25% of all liver cancers, representing the leading indication for liver transplantation. 1 – 3 Genotype 1 is the most common HCV genotype worldwide and includes 11 subgenotypes, of which 1a and 1b are responsible for the vast majority of infections. 4 Genotype 1b infection is the most prevalent form worldwide, particularly . . .