Interim data from Phase 2a hepatitis C ( HCV ) clinical trial that showed all patients ( 13/13 ) who reached the 4-week post-treatment follow-up had undetectable levels of hepatitis C virus ( SVR4 ) with an investigational, 12-week, all-oral regimen of Faldaprevir and Deleobuvir, in combination with pan-genotypic NS5A inhibitor, PPI-668, with Ribavirin, were presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases ( AASLD ).
The primary efficacy endpoint of this ongoing trial is sustained virologic response 12 weeks after completion of treatment ( SVR12 ).
An additional study arm evaluating the regimen without Ribavirin, which was added per protocol following initial results in the Ribavirin-containing arms, showed that after four weeks on treatment, 12/12 patients had hepatitis C virus levels below an amount that can be quantified ( LLOQ ).
This ongoing Phase 2a study is evaluating 36 treatment-naive genotype-1a HCV patients. Two thirds of patients have the difficult-to-treat CT or TT IL28B genotype. Previous studies have shown that presence of the CT and TT IL28B genotypes led to a reduced likelihood of achieving viral cure.
In addition, more than half the patients in the study ( 20/36 ) have pre-existing HCV mutations. These include the Q80K variant in 12 of these patients, all of which had virologic responses to the Faldaprevir-based triple direct-acting antiviral ( DAA ) regimen.
This study contains three arms: the first arm enrolled 12 patients and is evaluating Faldaprevir 120mg once-daily ( QD ), PPI-668 200mg once-daily ( QD ) and Deleobuvir 600mg twice-daily ( BID ) with Ribavirin; the second arm enrolled 12 patients and is evaluating Faldaprevir 120mg QD, PPI-668 200mg QD and Deleobuvir 400mg BID with Ribavirin; the third arm enrolled 12 patients and is evaluating Faldaprevir 120mg QD, PPI-668 200mg QD and Deleobuvir 600mg BID without Ribavirin.
All patients in the study have received at least 4 weeks of treatment and 97% ( 35/36 ) achieved LLOQ. To date, one patient who had pre-existing NS5A and NS5B mutations failed treatment. This patient had a partial response to treatment but developed viral breakthrough and was discontinued.
To date, there has been one treatment discontinuation due to adverse events. The patient self-discontinued at week 9 on treatment due to gastrointestinal side effects. This patient had undetectable levels of HCV RNA by day 10 of treatment. Overall, adverse events have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying Faldaprevir and Deleobuvir.
Benign bilirubin elevation ( unconjugated hyperbilirubinemia ) has been common in the trial and has occurred in 88% of patients in Ribavirin-containing arms, and 46% of patients in the Ribavirin-free arm.
In the ribavirin-free treatment arm, most adverse events ( 83% ) have been characterized as mild. In the Ribavirin-containing arms, adverse events have been mild to moderate. ( Xagena )
Source: Boehringer Ingelheim, 2013