Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial

Forns, Xavier; Lee, Samuel S.; Valdes, Joaquin; Lens, Sabela; Ghalib, Reem; Aguilar, Humberto; Felizarta, Franco; Hassanein, Tarek; Hinrichsen, Holger; Rincón, Diego; Morillas, Rosa; Zeuzem, Stefan; Horsmans, Yves; Nelson, David R.; Yu, Yao; Krishnan, Preethi; Lin, Chih‐Wei; Kort, Jens; Mensa, Federico

doi:10.1016/s1473-3099(17)30496-6

Cited by 316 publications

(280 citation statements)

References 19 publications

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“…Although new pangenotypic regimens, such as a combination of SOF and velpatasvir or glecaprevir and pibrentasvir, are available [20, 21], genotype-guided therapy, such as SOF plus RBV combination therapy for genotype 2 or DCV and ASV therapy for genotype 1b, was used as standard of care for patients with HCV infection in Japan between 2014 and 2016. The HCV genotype constituted an important viral factor for the selection of the appropriate DAA regimen and its duration in patients with chronic HCV infection when pangenotypic regimens were unavailable.…”

Section: Discussionmentioning

confidence: 99%

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy

et al. 2019

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Background: The incidence of mixed hepatitis C virus (HCV) genotype infection is variable, and a few reports exist regarding the efficacy of direct-acting antivirals (DAA) therapy for mixed genotype. We aimed to investigate the prevalence of mixed genotype and its impact on the virologic response to DAA therapy. Methods: A total of 365 patients with chronic HCV infection who completed antiviral therapy were recruited. Nested polymerase chain reaction with universal and specific primers of genotypes 1b and 2 and direct sequencing were used for HCV genotyping. Results: Direct sequencing with universal primers defined genotypes 1b (n = 230), 2a (n = 95), and 2b (n = 40). Direct sequencing of genotype 2 was performed in patients with genotype 1b, and direct sequencing of genotype 1b in patients with genotype 2. Four patients with genotype 1b underwent amplification for genotype 2, and direct sequencing identified genotypes 1b (n = 1), 2a (n = 1), and 2b (n = 2). None with genotype 2 underwent amplification for genotype 1b. Three cases were confirmed to have mixed genotype. Conclusions: Mixed genotype was rare, and hence the impact of mixed genotype on treatment outcome with DAA therapy is expected to be minimal.

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Section: Discussionmentioning

confidence: 99%

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy

et al. 2019

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“…In several registration studies, the 8-week duration of GLE/PIB achieved SVR in 98% to 99% of participants without cirrhosis, whereas the 12-week duration achieved SVR in 99% of participants with cirrhosis. 34–36 Advantages include the ability to use GLE/PIB in patients with renal dysfunction or end-stage renal disease without adjusting the dosage. One important limitation due to safety is that glecaprevir (and all HCV protease inhibitors) are not recommended in patients with decompensated liver disease because of the potential for hepatotoxicity.…”

Section: Proposed Framework For Simplified Management Of Hcv Infectiontmentioning

confidence: 99%

“…Although glecaprevir levels are decreased by proton pump inhibitors, proton pump inhibitor use did not affect response rates in the large Phase III trial, and no dose adjustment is recommended in the package insert. 33,36 …”

Section: Proposed Framework For Simplified Management Of Hcv Infectiontmentioning

confidence: 99%

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers

Kapadia

Marks

2018

Clinical Therapeutics

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This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.

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“…The EXPEDITION-1 study evaluated GLE/PIB for 12 weeks in GT1 infected patients with cirrhosis and 11 patients had previously failed a SOF + RBV regimen with or without peg-IFN. [23] The ENDURANCE-1 study evaluated 8 versus 12 weeks of GLE/PIB in patients without cirrhosis, but only 3 patients had previously failed a non-NS5A inhibitor, sofosbuvir-containing regimen. [24] Lastly, GLE/PIB for 12 weeks was evaluated in NS3/4A PI failures in the MAGELLAN-1 trial, which included SMV plus SOF failures.…”

Section: Current Strategies For Retreatmentmentioning

confidence: 99%

“…In addition, the phase 3 EXPEDITION-1 study enrolled patients with cirrhosis across multiple genotypes (including 31 patients infected with HCV GT2) to GLE/PIB for 12 weeks. [23] Within the overall study, 36 patients were treatment experienced, 11 of which were SOF failures. All patients with GT2 achieved SVR12 in the intention-to-treat analysis.…”

Section: Current Strategies For Retreatmentmentioning

confidence: 99%

Retreatment Options Following HCV Direct-Acting Antiviral Failure

Zuckerman

Chastain

Naggie

2017

Curr Treat Options Infect Dis

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OPINION STATEMENT Despite the excellent efficacy of direct acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options. While some patients may benefit from resistance testing after DAA therapy failure to select the optimal treatment and duration, newly approved salvage therapies are not significantly impacted by common mutations and have been approved by the Food and Drug Administration for HCV retreatment without regard for the presence of resistance associated substitutions. While prior retreatment efforts were limited to longer courses of therapy, the addition of ribavirin, or novel combinations of approved therapies based on expert guidance, current DAA options make HCV retreatment in the DAA era more streamlined and evidence-based.

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Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial

Cited by 316 publications

References 19 publications

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers

Retreatment Options Following HCV Direct-Acting Antiviral Failure

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