Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C

Aghemo, Alessio; Francesco, Raffaele De

doi:10.1136/gutjnl-2014-307958

Cited by 5 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These rates of SVR in GT 1 patients with DCV, PEG‐IFN and RBV, are similar to the efficacy rates reported by real‐life data on the first‐generation protease inhibitors, TPV and BOC, which achieved 68% and 56% SVR rates, respectively, in cohorts of patients enriched with factors associated with treatment failure, such as advanced fibrosis, older age and concomitant comorbidities . However, DCV clearly demonstrates an advantage over TPV and BOC in terms of safety and tolerability profiles . Higher SVR rates have been demonstrated when ASV is incorporated to the DCV/PEG‐IFN/RBV regimen …”

Section: Phase II Studiessupporting

confidence: 81%

“…This may be explained largely by a lower genetic barrier to resistance for DCV in GT1a as noted by higher on‐treatment virological failure due to emergence of DCV‐associated resistant variants (GT1a: 21% vs. GT1b: 8%) . These rates of SVR in GT 1 patients with DCV, PEG‐IFN and RBV, are similar to the efficacy rates reported by real‐life data on the first‐generation protease inhibitors, TPV and BOC, which achieved 68% and 56% SVR rates, respectively, in cohorts of patients enriched with factors associated with treatment failure, such as advanced fibrosis, older age and concomitant comorbidities . However, DCV clearly demonstrates an advantage over TPV and BOC in terms of safety and tolerability profiles .…”

Section: Phase II Studiessupporting

confidence: 77%

“…Notably, an important factor influencing treatment response that was alluded to during pre‐clinical studies and has been confirmed in Phase II studies is the difference in SVR between GT1a (55–57%) and GT1b (76–77%) patients treated with DCV . This may be explained largely by a lower genetic barrier to resistance for DCV in GT1a as noted by higher on‐treatment virological failure due to emergence of DCV‐associated resistant variants (GT1a: 21% vs. GT1b: 8%) . These rates of SVR in GT 1 patients with DCV, PEG‐IFN and RBV, are similar to the efficacy rates reported by real‐life data on the first‐generation protease inhibitors, TPV and BOC, which achieved 68% and 56% SVR rates, respectively, in cohorts of patients enriched with factors associated with treatment failure, such as advanced fibrosis, older age and concomitant comorbidities .…”

Section: Phase II Studiesmentioning

confidence: 94%

“…Patients with GT4 in the 20 mg, 60 mg and placebo groups achieved SVR24 rates of 67%, 100% and 50% respectively . Notably, an important factor influencing treatment response that was alluded to during pre‐clinical studies and has been confirmed in Phase II studies is the difference in SVR between GT1a (55–57%) and GT1b (76–77%) patients treated with DCV . This may be explained largely by a lower genetic barrier to resistance for DCV in GT1a as noted by higher on‐treatment virological failure due to emergence of DCV‐associated resistant variants (GT1a: 21% vs. GT1b: 8%) .…”

Section: Phase II Studiesmentioning

confidence: 97%

See 3 more Smart Citations

Review article: the efficacy and safety of daclatasvir in the treatment of chronic hepatitis C virus infection

Bunchorntavakul

Reddy

2015

Aliment Pharmacol Ther

View full text Add to dashboard Cite

Summary Background The treatment of hepatitis C virus (HCV) has evolved dramatically after the introduction of direct acting anti‐virals. NS5A protein plays an important role in HCV replication and is an attractive target for drug development. Aim To review clinical studies on the efficacy and safety of direct‐acting anti‐virals regimens containing daclastavir, an NS5A inhibitor, in the treatment of chronic hepatitis C. Methods A Medline search was undertaken to identify relevant literature using search terms including ‘daclatasvir’, ‘HCV treatment’ and ‘NS5A inhibitors’. Furthermore, we scanned abstracts presented at the recent international meetings in liver disease, viral hepatitis and infectious disease, as well as the reference lists of the review articles to identify publications not retrieved by electronic searches. Results Daclatasvir is the first‐in‐class HCV NS5A inhibitor that has been demonstrated in Phase I‐III trials to have a potent anti‐viral effect and clinical efficacy across multiple HCV genotypes (GT). Daclastavir is generally safe and well tolerated, with a low barrier to resistance and low potential for drug–drug interaction. When Daclastavir is added to PEG‐IFN/RBV platform, sustained virological response (SVR) rates are increased significantly compared with PEG‐IFN/RBV alone. The all‐oral combination of Daclastavir/asunaprevir (ASV; protease inhibitor) has high SVR rates against GT1b, but less activity against GT1a. Dual combination of Daclastavir/Sofosbuvir (SOF; nucleotide polymerase inhibitor) and triple combination of Daclastavir/ASV/beclabuvir (BCV; non‐nucleoside polymerase inhibitor) have demonstrated >90% SVR rates in both treatment naïve and treatment‐experienced patients with GT1. Furthermore, Daclastavir/SOF combination has also demonstrated up to 90% SVR rates in patients with GT3, and in those with human immunodeficiency virus coinfection, cirrhosis and post‐transplant HCV recurrence with any GT. Daclastavir/ASV/BCV has primarily demonstrated near 100% SVR rates in patients with GT4. Conclusion Daclastavir‐containing regimens, with or without PEG‐IFN, have shown promising results in clinical trials, and present an excellent treatment option for those with chronic HCV and for multiple genotypes.

show abstract

Section: Phase II Studiessupporting

confidence: 81%

Section: Phase II Studiessupporting

confidence: 77%

Section: Phase II Studiesmentioning

confidence: 94%

Section: Phase II Studiesmentioning

confidence: 97%

See 2 more Smart Citations

Review article: the efficacy and safety of daclatasvir in the treatment of chronic hepatitis C virus infection

Bunchorntavakul

Reddy

2015

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…Elimination of DCV is mainly fecal (88%) with a small amount excreted in urine. [37] In contrast, DCV exposure diminishes in patients with hepatic insufficiency, most likely as result of hypoalbuminemia, although the free concentration of the drug does not change much; therefore, no dose adjustment is recommended. DCV is a substrate for CYP3A4 and P-gp, and inhibits transporters organic anion transporting polypeptides 1/3 as well as P-gp.…”

Section: Drug–drug Interaction With Direct-acting Antiviralsmentioning

confidence: 99%

SASLT guidelines: Update in treatment of Hepatitis C virus infection

Alghamdi

Sanai

et al. 2016

Saudi J Gastroenterol

View full text Add to dashboard Cite

Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b

Flisiak

Kawazoe²,

Znoyko

et al. 2016

Journal of Interferon & Cytokine Research

View full text Add to dashboard Cite

The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir (Lambda/RBV/DCV), versus peginterferon alfa-2a combined with ribavirin/telaprevir (Alfa/RBV/TVR), in patients chronically infected with hepatitis C virus (HCV), genotype 1b. This was a prospective, randomized, open-label, phase 3 study (NCT01718158) in adults (aged ≥18 years) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy. The primary endpoint was sustained virologic response at post-treatment follow-up week 12 (SVR12). Patients were randomized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR. Overall, 440 patients were treated (294 with Lambda/RBV/DCV; 146 with Alfa/RBV/TVR). The proportion of patients achieving SVR12 was 88.8% in the Lambda/RBV/DCV arm and 70.5% in the Alfa/RBV/TVR arm (difference between arms: 18.3%; 95% confidence interval: 9.9-25.7; P < 0.0001). Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events (AEs), cytopenic abnormalities, flu-like symptoms, serious AEs, and discontinuations due to AEs, but more liver abnormalities than those in the Alfa/RBV/TVR group. In conclusion, treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV, genotype 1b infection.

show abstract

Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C

Cited by 5 publications

References 11 publications

Review article: the efficacy and safety of daclatasvir in the treatment of chronic hepatitis C virus infection

Review article: the efficacy and safety of daclatasvir in the treatment of chronic hepatitis C virus infection

SASLT guidelines: Update in treatment of Hepatitis C virus infection

Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b

Contact Info

Product

Resources

About