Study results presented at The Liver Meeting 2012 show the experimental treatment leads to high rates of viral clearance in patients with hepatitis C, even in those with compensated cirrhosis.
The experimental protease inhibitor faldaprevir, in combination with a non-nucleoside NS5B inhibitor BI 217127 plus ribavirin, leads to high rates of viral clearance in patients with hepatitis C, even in those with compensated cirrhosis, according to data presented at The Liver Meeting, the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
The results showed that sustained viral reduction at 12 weeks post-treatment (SVR12) was achieved in up to 69% of patients receiving the three drugs, versus only 39% in patients receiving the two experimental compounds but not ribavirin.
The Phase II trial, called SOUND-C2, was one of the largest trials to date of the new generation of antivirals, enrolling 362 patients. The study was sponsored by Boehringer Ingelheim, and presented by Stefan Zeuzem, MD, of the J.W. Goethe University Hospital, Frankfurt, Germany.
“This trial was one of the rare interferon-free trials so far open to patients with compensated cirrhosis,” Zeuzem said.
Patients were randomized to 1 of 5 treatment arms, which varied by duration and dose. Arms 1 through 4 administered all three drugs. In arm 1, patients received BI 217127 BID and were treated for 28 weeks, while in arms 2 through 4, they received it TID and were treated for 16, 28, or 40 weeks.
The 5th arm withheld ribavirin, but was stopped early by regulatory authorities due to poor viral control. “Ribavirin remains a necessary component of therapy,” Zeuzem said.
SVR12 rates for arms 1 through 4 on an intent-to-treat basis were 59%, 59%, 52%, and 69%. When response rates were analyzed on a per-protocol basis, however, all four arms performed roughly equally, with an approximately 69% response rate.
Overall the drugs were well tolerated and safe, Zeuzem said. There was a slightly higher rate of moderate adverse events in the arms receiving BI 217127 TID, “suggesting there is an advantage from a patient tolerability perspective of BID dosing” over TID dosing of the non-nucleoside inhibitor.
There were no discontinuations for “signature” adverse events of interest, including nausea, vomiting, rash, and asthenia. The best tolerated regimen was arm 3, with 28 weeks of BID dosing. Lab profiles indicated the drugs were safe, with an increase in indirect bilirubin the only abnormality. One patient experienced a relapse at 36 weeks, Zeuzem reported.
The best response to treatment was seen in patients with viral genotype 1b versus 1a, with an odds ratio of 6.33, “a huge difference,” Zeuzem said. Eighty-five percent of patients with the 1b genotype achieved SVR12, despite that the group contained a significant number of cirrhotic patients.
IL28b patient genotype also influenced response, with a response rate of 84% for the CC genotype versus 64% for the non-CC genotype (odds ratio 4.54).
Surprisingly, female sex and normal baseline GGT levels were also associated with better response, though the differences were smaller.
The combination of the two experimental drugs plus ribavirin is now proceeding to a Phase III trial, according to Zeuzem.