Eric Lawitz from the University
of Texas Health Science Center and colleagues evaluated ABT-493 and ABT-530 as
monotherapy for people with previously untreated HCV genotype 1, with or without
compensated liver cirrhosis.
This open-label phase 2 dose-ranging study
enrolled a total of 89 participants. About 75% were men, most were white and
the mean age was approximately 55 years. More than 80% had harder-to-treat HCV
Groups of eight people without cirrhosis were
allocated to receive ABT-493 at doses of 100, 200, 300, 400 or 700mg, once daily for three
days; people with cirrhosis received only the 200mg dose. Similarly, separate
groups of eight people without cirrhosis received ABT-530 at doses of 15, 40, 120 or
400mg once-daily for three days; people with cirrhosis received only the 120mg
dose. After three days, everyone started the Viekirax
+ Exviera regimen.
For ABT-493 monotherapy, the mean maximal HCV viral load decreases over three
days ranged from -3.8 to -4.3 log IU/ml,
with no significant differences across dose groups. There was also no
significant difference in HCV RNA decreases between people with or without
For ABT-530 monotherapy, the mean maximal viral load decreases ranged from -3.4 to -4.5 log IU/ml, and from -3.9 to -4.3 log IU/m using the selected
40mg dose. All higher doses produced significantly larger decreases than the 15mg
dose, but no greater potency was
seen at doses over 40mg. Maximal viral load decreases were slightly higher
among people without cirrhosis compared to people with cirrhosis (-4.1-4.5 vs -3.9 among
those receiving 40mg).
For both drugs, the largest HCV RNA decreases were seen during the first
24 hours, with smaller incremental decreases during days 2 and 3.
ABT-493 and ABT-530 were both generally safe and well-tolerated. Forty-five per cent of people receiving ABT-493 and 25% of those receiving ABT-530 experienced
treatment-emergent adverse events, mostly mild.
The most common adverse events with ABT-493 were headache (22%),
abdominal discomfort (6%), diarrhoea (6%), fatigue (6%) and rash (6%). The most
common side-effects with ABT-530 were headache (10%), constipation (5%) and
(5%). No clinically significant laboratory abnormalities were attributed
to either drug.
"In this phase 2, open-label, dose-ranging trial, three-day
monotherapy with ABT-493 or ABT-530 resulted in robust plasma HCV RNA declines
from baseline in treatment-naive patients with HCV genotype 1 infection with
and without compensated cirrhosis," the researchers concluded.
While a formal comparison between people with HCV subtypes 1a and 1b
was not possible due to the small number of people with 1b, viral load declines
be similar," they added.