An interferon-free combination of three drugs plus ribavirin
achieved a sustained virologic response (SVR12) in 96% of previously untreated
patients with genotype 1 hepatitis C infection, AbbVie reported in a press
release on Monday 18 November.
The results are the first in a sequence of six announcements
of the results of phase III studies due to take place over the next few months,
prior to presentation of the full results at scientific meetings in 2014.
On the basis of these results AbbVie plans to file for registration of the combination in
the United States and European Union in the second quarter of 2014, and hopes
to have the first interferon-free combination for the treatment of genotype 1
hepatitis C infection available for prescription by early 2015.
The regimen consists of a fixed dose combination tablet
containing the NS5A inhibitor ABT-267 and ABT-450 boosted by ritonavir, dosed
once daily, and a second tablet, the non-nucleoside polymerase inhibitor ABT-333,
dosed twice daily. The combination is being tested with and without ribavirin
to determine whether it is possible to cure hepatitis C infection without the
need for ribavirin, which can cause anaemia.
The SAPPHIRE 1 study released this week represents an
easier-to-treat population of patients without cirrhosis. The study recruited
631 patients with genotype 1a or 1b hepatitis C and randomised them to receive
either ABT-450 boosted by ritonavir, ABT-333 and ABT-267, or a placebo, for 12
weeks. Patients in the placebo group received the active treatment after 12
weeks.
The headline results showed that 96% of the study population
achieved SVR12, and only 1.7% of participants experienced virologic relapse after
completing treatment. There was little difference in virologic response by
sub-genotype: 95% of genotype 1a and 98% of genotype 1b patients achieved
SVR12. Treatment discontinuations due to adverse events were rare (0.6%) and
the main side-effects reported by patients were nausea, headache and fatigue.
Further phase III studies will report on the efficacy of the
combination in treatment-experienced patients, and also determine whether there
are differences between genotypes 1a and 1b and between treatment-naïve and
treatment-experienced patients in their need for ribavirin. The Turquoise study
is comparing 12 and 24-week ribavirin-containing regimens in genotype 1
patients, including those with cirrhosis.
AbbVie is also conducting phase II studies of a once-daily two-drug
combination, of ABT-450/r and ABT-267, and reported the first results
from these studies at the Liver Meeting earlier this month.