Across all cohorts,
treatment with MK-5172 plus MK-8742 was generally
safe and well-tolerated. Frequency of serious adverse events ranged from none
to 7%, and there were few or no discontinuations due to adverse events. The
most common side-effects were fatigue, headache, nausea, diarrhoea, insomnia
and weakness. Anaemia occurred in about 5 to 10% of people taking ribavirin, but not
in people taking the dual regimen.
Hezode's team concluded,
"A 12-week regimen of MK-5172 + MK-8742 with or without
ribavirin is a highly efficacious, safe, well-tolerated, all-oral regimen with
once-daily dosing." Hezode added that "ribavirin is not needed
regardless of HCV genotype 1 subtype."
"MK-5172 + MK-8742 +/- ribavirin
demonstrated high efficacy," Lawitz's team summarised. "In
treatment-naive patients with cirrhosis, high efficacy was achieved regardless
of use of ribavirin or extended treatment duration. In prior null responder
patients, a 12-week ribavirin-free regimen resulted in >90% SVR4-SVR8."
Sulkowski's group concluded that,
"Safety, tolerability and efficacy in co-infected patients was similar to
other patient populations in C-WORTHY."
Good response rates for people with HIV in
several studies of direct-acting antivirals have led several experts to suggest
that people with HIV and hepatitis C co-infection no longer need be considered a 'special' or
difficult-to-treat population, as long as drug interactions with antiretrovirals
are taken into account.
These results "support the hypothesis
that HIV co-infection is not associated with poorer response to all-oral
regimens," Sulkowski said. In fact, people with HIV on suppressive ART are
known to have good adherence, which may predict future adherence to hepatitis C
treatment as well. He added, however, that MK-5172 affects the CYP3A4 enzyme,
so it could be "potentially problematic" with regard to interactions
with certain antiretrovirals and other medication classes.
These findings support ongoing phase 3
clinical trials testing MK-5172 + MK-8742 with or without ribavirin in various
patient populations. Lawitz noted that a co-formulation of the two Merck drugs
is being developed.