January 2015 for the treatment of adults with chronic hepatitis C
infection. The German Institute for Quality and Efficiency in Health
Care (IQWiG) examined in a dossier assessment whether this drug offers
an added benefit over the appropriate comparator therapy.
According to the findings, there are indications of an added benefit
in patients who have not yet developed cirrhosis of the liver and who
are infected with the hepatitis C virus (HCV) genotype 1a. In case of
genotype 1b, this only applies to treatment-naive, but not to
treatment-experienced patients. The extent of added benefit is
non-quantifiable, however. No added benefit can be derived from the
dossier for seven other Patient groups.
Differentiated approvals result in a large number of patient groups
Dasabuvir is only approved in combination with other drugs
(ombitasvir/paritaprevir/ritonavir and/or ribavirin). The Summaries of
Product Characteristics specify partly different treatment regimens both
for these drugs or drug combinations and for the respective comparator
therapies. This results in as many as ten patient groups for this
benefit assessment, which mainly differ in type of virus, pretreatment
and stage of disease.
Two direct comparative studies
All ten groups were reflected in the dossier compiled by the drug
manufacturer, but the data were informative for only three of these
groups. The benefit assessment was based on two randomized controlled
approval studies (MALACHITE I and II), in which dasabuvir in combination
with ombitasvir/paritaprevir/ritonavir and/or ribavirin was directly
compared with triple therapy consisting of telaprevir, pegylated
interferon and ribavirin.
In compliance with the approval, the new fixed-dose combination was
administered in the intervention arm for a period of 12 weeks, whereas
treatment in the comparator arm could last up to 48 weeks, depending on
response to the treatment.
Patients in the intervention arm were free of the virus more frequently
These two studies provided conclusive results for patients who have
not yet developed cirrhosis of the liver and who are infected with a
virus of genotype 1a or 1b. In genotype 1a, this applies both to
treatment-naive patients and to patients who had relapsed after
initially successful treatment. In genotype 1b, appropriate data were
available only for treatment-naive patients.
In these three patient groups, the data showed a statistically
significant difference in sustained virologic response (SVR) in favour
of the new fixed-dose combination. IQWiG derived an indication of an
added benefit from this. Its extent is non-quantifiable, however. It
remained unclear in how many patients in whom the virus is no longer
detectable, late complications, and liver cancer in particular, can
actually be prevented.
Quality of life: advantage in treatment-naive patients
For the first time in the assessment of a hepatitis C drug, the
manufacturer dossier contained evaluable data on health-related quality
of life, which is of particular importance regarding interferon, which
is considered to be very burdensome. These data on quality of life
showed an advantage of dasabuvir at least for the duration of treatment.
This applies to certain treatment-naive genotype 1a or 1b patients, but
not to treatment-experienced patients (genotype 1a). It depends on the
severity of the disease whether they have an advantage and how big this
IQWiG derived a hint of an added benefit with differing extent from these data.
Data on side effects partly not conclusively interpretable
The important differences in treatment duration between intervention
and control arm, which could be up to 36 weeks, partly made it
impossible to interpret differences in side effects. Since the
observation periods also differed, the results were probably biased.
Regarding the robustness of the data, however, there were exceptions
in certain patient groups or aspects of side effects (serious adverse
events and treatment discontinuation). In each case, the results were in
favour of the new fixed-dose combination.
IQWiG therefore sees a hint or an indication of lesser harm in
treatment-naive genotype 1b patients and an indication of lesser harm in
treatment-experienced genotype 1a patients for individual aspects of
side effects. Overall, greater or lesser harm is not proven.
Robust data were lacking for further patient groups
The dossier contained no suitable data for the remaining seven
patient groups (genotype 1). Since direct comparative studies were
lacking, the manufacturer referred to results on dasabuvir, in which the
drug was not tested against the appropriate comparator therapy,
however. No systematic comparison with data on the appropriate
comparator therapy was conducted. Since there was also no systematic
search for studies on the comparator therapies, it can be assumed that
the data were incomplete.
Overall, an indication of a non-quantifiable added benefit can be
derived from the dossier for three patient groups: patients without
cirrhosis of the liver infected with genotype 1a (treatment-naive and
treatment-experienced) and with genotype 1b who have not been
G-BA decides on the extent of added benefit
This dossier assessment is part of the early benefit assessment
according to the Act on the Reform of the Market for Medicinal Products
(AMNOG) supervised by the G-BA. After publication of the dossier
assessment, the G-BA conducts a commenting procedure and makes a final
decision on the extent of the added benefit.
An overview of the results of IQWiG’s benefit assessment is given by
a German-language executive summary. In addition, the website » http://www.gesundheitsinformation.de, published by IQWiG, provides easily understandable German-language information.
More English-language information will be available soon (Sections
2.1 to 2.7 of the dossier assessment as well as subsequently published
health information on » http://www.informedhealthonline.org). If you would like to be informed when these documents are available, please send an e-mail to » email@example.com.