Generic sofosbuvir-based
combinations may not perform as well as therapy based on branded
sofosbuvir-containing regimens, according to result of a study conducted in
Qatar and presented to the recent 2016 AASLD Liver Meeting. People treated with generics
were less likely to have a sustained virological response 12-weeks post
treatment (SVR12) and were also more likely to experience an adverse event,
compared to people who received branded drugs.
But the
investigators speculate that the generics may have under-performed because of
the high proportion of people treated with suboptimal regimens, and believe
this deserves further research.
In Qatar, between
0.5 and 1.1% of the local population have chronic hepatitis C virus (HCV) infection, though the
prevalence is much higher – 6.3% – among
migrants. Sofosbuvir is approved in Qatar for use in interferon-containing and
all oral combinations. The country aims to control its HCV epidemic by 2020.
However, providing therapy for migrants has been challenging because of
restrictions on drug reimbursement costs. Therefore, the treatment of migrants who have HCV infection is relying on the use of generics.
Because of this
reliance on generics, investigators designed an observational study comparing
the efficacy and safety of HCV treatment regimens based on branded or generic
sofosbuvir. Local patients were provided with the branded versions of anti-HCV
drugs by their hospital, whereas migrants were required to obtain generics via other
sources.
The primary
outcomes were SVR12 and drug safety.
The study
population consisted of 343 people, with 38% treated with branded medication
and 62% with generics. People treated with generics were younger (49 vs 51
years, p = 0.019) and more likely to be male (85% vs 54%, p < 0.001)
compared to individuals provided with branded drugs.
The most commonly
used combination was sofosbuvir/simeprevir (35%), followed by
sofosbuvir/ribavirin (24%), sofosbuvir/interferon/ribavirin (21%),
sofosbuvir/ledipasvir (11%), sofosbuvir/daclatasvir (10%),
sofosbuvir/ledipasvir/ribavirin (0.6%) and sofosbuvir/interferon (0.3%).
SVR12 data were
available for 251 people.
Overall, the
branded medication significantly out-performed generics (SVR12 = 91% vs. 74%, p
= 0.001). However, among people taking sofosbuvir/simeprevir, the group
taking the generics were slightly more likely to attain a SVR12 than those
taking branded drugs (95% vs. 90%).
Outcomes for
people taking sofosbuvir/ribavirin were especially poor, regardless of
whether the branded or generic drugs was used (75% vs. 64%).
Other factors
associated with the chances of attaining SVR12 were gender (female, 91% vs male,
78%, p = 0.017), HCV genotype (G1, 92% vs G4, p = 0.041) and cirrhosis status
(no cirrhosis, 86% vs cirrhosis, 74%, p = 0.049).
An adverse event
was observed in 16% of people overall. But individuals treated with generics
were more likely to experience an adverse event compared to those treated
with the branded drug (20% vs 10%, p = 0.001).
The most common
adverse events were anaemia (4%), increased bilirubin and fatigue (2%),
headache (2%), and cough, skin rash and hepatocellular carcinoma (1%).
“In this study,
brand-name products showed better effectiveness and safety than generic
medications,” conclude the authors. “This observation, though probably driven
by the high number of patients on suboptimal regimens such as
sofosbuvir/ribavirin and sofosbuvir/interferon/ribavirin, should be explored in
future studies."