Клинические испытания "безинтерферонного" лечения гепатита C
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.
AbbVie plans to file for registration of the combination in the United States and the 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 participants 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. Participants 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-naive 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 2013, held earlier this month.