4 Once Daily Alisporivir (Deb025) Plus Pegifnalfa2a/Ribavirin Results in Superior Sustained Virologic Response (Svr24) in Chronic Hepatitis C Genotype 1 Treatment Naive Patients

Flisiak, Robert; Pawlotsky, Jean‐Michel; Crabbé, R.; Calistru, Petre Iacob; Kryczka, Wiesław; Häussinger, Dieter; Mazzella, Giuseppe; Romero‐Gómez, Manuel; Purcea, Daniela; Vuagniaux, Grégoire; Bao, Weibin; Avila, Claudio; Zeuzem, Stefan

doi:10.1016/s0168-8278(11)60006-8

Cited by 51 publications

(34 citation statements)

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“…A phase 2 trial demonstrated the superiority of alisporivir when administered once a day with peg-IFN/ribavirin in achieving SVR in genotype 1 CHC patients. The triple therapy showed 76% SVR compared with 55% in the peg-IFN/ribavirin control arm, and only 24 weeks treatment duration needed for SVR in patients with RVR 64. One case of SVR in a genotype 3 CHC patient was reported after alisporivir monotherapy for 29 days 65…”

Section: Hcv Life Cycle: Novel Agents In Clinical Developmentmentioning

confidence: 98%

New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

Welsch

Jesudian

Zeuzem

et al. 2012

Gut

176

117

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Until recently, the standard of care (SOC) for patients with chronic hepatitis C virus (HCV) infection has consisted of a combination of pegylated interferon-α [corrected] plus ribavirin, administered for 24- to 48-weeks depending on the HCV genotype. The sustained virologic response rate for this SOC has been only about 50% in patients infected with genotype 1 HCV, the most prevalent genotype in Europe and North America. HCV therapy has been revolutionised recently by the approval of two direct-acting antiviral agents (DAA) against the NS3/4A serine protease for use in genotype 1 HCV, the ketoamide inhibitors boceprevir and telaprevir. The novel SOC marks the beginning of an extraordinary new era in HCV therapy. We review this new SOC with an emphasis on practical issues related to protease inhibitors, e.g. prescribing guidelines, futility rules and management of adverse events. We also give a perspective on what to expect in the coming years. Newer DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in most if not all CHC patients who undergo treatment. The novel agents in clinical development are paving the way for future interferon-sparing regimens.

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Section: Hcv Life Cycle: Novel Agents In Clinical Developmentmentioning

confidence: 98%

New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

Welsch

Jesudian

Zeuzem

et al. 2012

Gut

176

117

View full text Add to dashboard Cite

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“…Very low viral breakthroughs arose in CypItreated patients such as alisporivir-treated patients ). Viral breakthrough was only observed in TT or CT IL28B allele patients in the alisporivir ESSENTIAL study (Flisiak et al 2011). Population sequencing of HCV genomes did not identify any genotypic change consistently associated with viral breakthrough, assessed by clonal sequencing of NS5A, the putative in vivo viral target of CypA.…”

Section: Nim811mentioning

confidence: 82%

“…In the ESSENTIAL study (Flisiak et al 2011), all treatment-naïve genotype 1 patients (n = 288) received pegylated IFNa and ribavirin. In arm 1, patients received placebo once daily for 48 weeks.…”

Section: Nim811mentioning

confidence: 99%

Resistance to Cyclophilin Inhibitors

Gallay

2014

Handbook of Antimicrobial Resistance

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The best approach to avoid hepatitis C virus (HCV) resistance to a specific therapy is rapid and massive suppression of viral replication. This is best accomplished by combining several drugs with potent antiviral activity across multiple genotypes, with each possessing a high barrier to resistance, different mechanisms of action, and no cross-resistance. A novel class of anti-HCV agents that have shown great promise in HCV patients -the cyclophilin inhibitors (CypI) -possess such properties. CypI are host-targeting antivirals (HTAs) with a mechanism of action that differs from those of all existing direct-acting antivirals (DAAs). CypI are pan-genotypic due to their distinct mechanism of action that targets the host protein cyclophilin A (CypA), which is required for HCV replication. HCV has to develop a lengthy mutational strategy to efficiently replicate in vitro independently of the host factor CypA leading to a high genetic barrier that the virus has to cross to develop resistance to CypI. CypI mediate rapid and profound viral load suppression in patients. Very low viral breakthrough rates are associated with the CypI treatment, which result mostly from suboptimal drug exposure rather than viral resistance. The high genetic barrier and the lack of cross-resistance to DAAs make CypI attractive drug candidates to be part of a regimen with one or two DAAs that may constitute the backbone of a new, safe, and effective IFN-free therapy. The characteristic resistance profile of CypI offers an exceptional opportunity to cure HCV. KeywordsHepatitic; cyclophilin; cyclophilia inhibitas; NSSA; resistance Abbreviations BIDTaken twice a day cEVR Complete early virological response = no virus detected after 12 weeks eRVR Extended rapid virological response = no virus detected at week 4 and week 12 EVR Early virological response = 2 log drop of HCV RNA after 12 weeks QD Taken once a day RVR Rapid virological response = no virus detected at week 4 SVR12 Sustained virological response = no virus detected at 12 weeks after completion of treatment SVR24 No virus detected at 24 weeks after completion of treatment

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“…Clinical studies have shown an increased incidence of hyperbilirubinaemia in patients treated with the cyclophilin inhibitor alisporivir compared with controls [54,55]. This may be due to the inhibition of the multidrug resistance protein 2 (MRP2) transporter by alisporivir [56], resulting in reduced elimination of conjugated bilirubin.…”

Section: Other Directly Acting Antivirals In Developmentmentioning

confidence: 99%

Directly acting antivirals for hepatitis C and antiretrovirals

Seden

Back²

2011

Current Opinion in HIV and AIDS

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As a result of DDIs, the concomitant use of some medicines with DAA will be contraindicated, whereas other combinations may require caution, monitoring, or dose modification of the co-administered drug. Management of DDIs with these novel agents will pose a new challenge, and prescriber awareness of the potential for DDIs is fundamental for safe prescribing. Online resources are likely to play a key role in prescriber education and clinical decision-making.

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4 Once Daily Alisporivir (Deb025) Plus Pegifnalfa2a/Ribavirin Results in Superior Sustained Virologic Response (Svr24) in Chronic Hepatitis C Genotype 1 Treatment Naive Patients

Cited by 51 publications

References 0 publications

New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

New direct-acting antiviral agents for the treatment of hepatitis C virus infection and perspectives

Resistance to Cyclophilin Inhibitors

Directly acting antivirals for hepatitis C and antiretrovirals

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