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.
EASL is
also encouraging European physicians to combine products from different
pharmaceutical companies to achieve the most potent interferon-free
regimens, often in advance
of full phase III trial data, in its new hepatitis C treatment
guidelines issued on Friday at the International Liver Congress in
London.
The guidelines move beyond US recommendations issued in
January, which incorporated a small number of off-label uses not
included in
the US licenses for sofosbuvir and simeprevir. The new guidelines also
include daclatasvir, an NS5A inhibitor that is likely to receive approval
in Europe later this year.
Guidelines panel chair Professor 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 Dr 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 people 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 one company.
The guidelines make recommendations for all genotypes, and
include all direct-acting antivirals that are expected to be licensed in Europe
during 2014, including the protease inhibitor simeprevir (Olysio) and the NS5A inhibitor daclatasvir. Simeprevir is likely to
receive marketing approval in May 2014 and daclatasvir in September 2014.
Bristol-Myers Squibb, the developer of daclatasvir, has anticipated the European
move towards a 'mix-and-match' approach by applying for a licence for daclatasvir
alone in Europe. In the United States, it is seeking a licence for daclatasvir
in combination with asunaprevir.
The guidelines recommend that the first-generation protease
inhibitors telaprevir or boceprevir should be used for treatment of genotype 1
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 2015.
The full guidelines can be downloaded from the EASL
website here.
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
|
Peg IFN/ribavirin + sofosbuvir
12 weeks (A1)
|
Previously untreated & prior relapsers: Peg IFN/ribavirin + simeprevir: 12 weeks, followed by 12
weeks of peg IFN/ribavirin (A1)
Previous partial responders & null-responders: Peg IFN/ribavirin
+ simeprevir: 12 weeks, followed
by 36 weeks of peg IFN/ribavirin (B1)
|
Sofosbuvir & simeprevir:
12 weeks. (Ribavirin may be added in previous non-responders and people with cirrhosis.)
(B1)
|
Sofosbuvir & daclatasvir:
12 weeks in previously untreated; 24 weeks in treatment-experienced patients.
(Ribavirin may be added in previous non-responders and people with cirrhosis.) (B1)
|
Peg IFN/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 IFN-free
option available (B2)
|
Genotype 2
|
Sofosbuvir &
ribavirin: 12 weeks (16-20 weeks in people with cirrhosis, especially
treatment-experienced). (A1)
|
Peg IFN/ribavirin + sofosbuvir
12 weeks for people with cirrhosis and/or treatment-experienced patients (B1)
|
Genotype 3
|
Sofosbuvir &
ribavirin: 24 weeks (unsuitable for treatment-experienced people with cirrhosis, no
specific alternative proposed). (A2)
|
Peg IFN/ribavirin + sofosbuvir
12 weeks (A2)
|
Sofosbuvir & daclatsvir
12 weeks (24 weeks for treatment-experienced patients) (B1)
|
Genotype 4
|
Peg IFN/ribavirin + sofosbuvir
12 weeks (B1)
|
Peg IFN/ribavirin + simeprevir:
12 weeks, followed by 12 weeks of peg
IFN/ribavirin (B1)
Previous partial responders & null-responders: Peg IFN/ribavirin
+ simeprevir: 12 weeks, followed
by 36 weeks of peg IFN/ribavirin (B1)
|
Peg IFN/ribavirin + daclatasvir;
12 or 24 weeks
(response-guided therapy) (B1)
|
Sofosbuvir & ribavirin
24 weeks for interferon-intolerant patients (C2)
|
Sofosbuvir & simeprevir:
12 weeks. (Ribavirin may be added in previous non-responders and people with cirrhosis.)
(B2)
|
Sofosbuvir & daclatasvir:
12 weeks in previously untreated; 24 weeks in treatment-experienced patients.
(Ribavirin may be added in previous non-responders and people with cirrhosis.) (B2)
|
Genotype 5 or 6
|
Peg IFN/ribavirin + sofosbuvir
12 weeks (B1)
|
Sofosbuvir &
ribavirin: 12 weeks (C2)
|