EASL 2014: European Liver Specialists Recommend Use of Newest Hepatitis C Drugs

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The European Association for the Study of the Liver (EASL) has issued new guidelines for the treatment of hepatitis C, which recommend that wherever possible, patients should be treated with the newest direct-acting antivirals. The guidelines also recommend physicians should "mix and match" antivirals from different companies to get the most potent regimens.

[Produced in collaboration with Aidsmap and infohep]

The panel that developed the guidelines discussed their recommendations and implications for hepatitis C treatment in Europe and worldwide at EASL's International Liver Congress this week on London. The full guidelines can be downloaded from the EASL website.

The guidelines move beyond U.S. recommendations issued in January, which incorporated a small number of off-label uses not included in the FDA licenses for sofosbuvir (Sovaldi) and simeprevir (Olysio). The new EASL guidelines also include daclatasvir, a NS5A inhibitor that is likely to receive approval in Europe later this year.

EASL is encouraging European physicians to combine products from different pharmaceutical companies to achieve the most potent interferon-free regimens, often in advance of full Phase 3 trial data.

Guidelines panel chair Jean-Michel Pawlotsky, director of the French National Reference Centre for Viral Hepatitis B, C and Delta, told reporters that the EASL guidelines were designed to accommodate the diversity of European populations and reimbursement practices. The guidelines were also designed to empower physicians to obtain permission to use new agents under compassionate access arrangements prior to licensing, said Alessio Aghemo, a member of EASL’s Scientific Committee and a professor of medicine at the University of Milan.

The EASL guidelines are another sign that when making prescribing decisions for patients with hepatitis C, physicians do not intend to be constrained by licensing indications or the quest of pharmaceutical companies to deliver "exclusive" drug combinations that require prescribers to use co-formulated direct-acting antivirals from a single company.

The guidelines make recommendations for all HCV genotypes, and include all direct-acting antivirals that are expected to be licensed in Europe during 2014, including the HCV protease inhibitor simeprevir and the NS5A inhibitor daclatasvir. Simeprevir is likely to receive marketing approval in May 2014 and daclatasvir in September 2014. Sofosbuvir was already approved in January 2014.

Bristol-Myers Squibb, the developer of daclatasvir, has anticipated the European move towards a "mix and match" approach by applying for a license for daclatasvir alone in Europe. In the U.S., it is seeking a license for daclatasvir in combination with its protease inhibitor asunaprevir.

The EASL guidelines recommend that the first-generation protease inhibitors telaprevir (Incivek or Incivo) or boceprevir (Victrelis) should be used for treatment of genotype 1 HCV infection only when newer options are not available. For other genotypes, the combination of pegylated interferon and ribavirin is described as "acceptable" where newer options are not available.

The guidelines will be updated as soon as approval dates for new interferon-free combinations of sofosbuvir/ledipasvir (Gilead Sciences) and ABT-450/ritonavir, ombitasvir, and dasabuvir (AbbVie) are known. These are likely to be approved in early 2014.

EASL 2014 recommendations for use of new direct-acting antivirals receiving European approval in 2014

Recommendations ranked by strength of clinical trial evidence (A1-C2)

GENOTYPE

OPTIONS FOR THERAPY

Genotype 1

PegIFN/ribavirin + sofosbuvir 12 weeks (A1)

Previously untreated & prior relapsers: PegIFN/ribavirin + simeprevir: 12 weeks, followed by 12 weeks of peg IFN/ribavirin (A1)

Previous partial responders & null-responders: PegIFN/ribavirin + simeprevir: 12 weeks, followed by 36 weeks  of peg IFN/ribavirin (B1)

Sofosbuvir + simeprevir: 12 weeks. (ribavirin may be added for previous non-responders & cirrhotics) (B1)

Sofosbuvir + daclatasvir: 12 weeks in previously untreated; 24 weeks in treatment-experienced patients. (ribavirin may be added in previous non-responders & cirrhotics). (B1)

PegIFN/ribavirin + daclatasvir 12 weeks(genotype 1b only) (B1), followed by 12 weeks  of peg IFN/ribavirin(B2)

Sofosbuvir + ribavirin 12 weeks for interferon-intolerant patients only, where no other interferon-free option available (B2)

Genotype 2

Sofosbuvir+ ribavirin: 12 weeks (16-20 weeks in cirrhotic patients, especially treatment-experienced) (A1)

PegIFN/ribavirin + sofosbuvir 12 weeks for cirrhotic and/or treatment-experienced patients (B1)

Genotype 3

Sofosbuvir+ ribavirin: 24 weeks (unsuitable for treatment-experienced cirrhotics, no specific alternative proposed). (A2)

PegIFN/ribavirin + sofosbuvir 12 weeks (A2)

Sofosbuvir + daclatasvir12 weeks (24 weeks for treatment-experienced patients) (B1)

Genotype 4

PegIFN/ribavirin + sofosbuvir 12 weeks (B1)

Peg FN/ribavirin + simeprevir: 12 weeks, followed by 12 weeks  of pegIFN/ribavirin (B1)

Previous partial responders & null-responders: PegIFN/ribavirin + simeprevir: 12 weeks, followed by 36 weeks  of peg IFN/ribavirin (B1)

Peg IFN/ribavirin + daclatasvir; 12 or24 weeks (response-guided therapy) (B1)

Sofosbuvir + ribavirin24 weeks for interferon-intolerant patients (C2)

Sofosbuvir + simeprevir: 12 weeks. (ribavirin may be added in previous non-responders and cirrhotics) (B2)

Sofosbuvir + daclatasvir: 12 weeks in previously untreated; 24 weeks in treatment-experienced patients. (ribavirin may be added in previous non-responders and cirrhotics). (B2)

Genotype 5 or 6

PegIFN/ribavirin + sofosbuvir 12 weeks (B1)

Sofosbuvir+ ribavirin: 12 weeks (C2)

4/13/14

Reference

European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C. http://files.easl.eu/easl-recommendations-on-treatment-of-hepatitis-C/index.html. April 2014.

Other Source

European Association for the Study of the Liver. EASL publishes on-line recommendations on the management of hepatitis C. Press release. April 9, 2014.