Shorter Treatment Shows Promise With Investigative HCV Agents

Can outcomes be sustained with shorter regimens?

A new study suggests that some subgroups of patients with hepatitis C virus infectioncan achieve sustained virologic responses (SVR) in as short as 4 weeks using an aggressive, investigational three-drug regimen, researchers reported here.

In the 4-week duration part of a multi-arm clinical trial, Eric Lawitz, MD, vice president of the Texas Liver Institute, San Antonio, reported that all 31 noncirrhotic genotype 1 hepatitis C virus-infected patients achieved undetectable virus at follow-up week two — but by week eight, 19 of those patients had relapsed, giving an SVR rate of 38.7%.

Among the 30 patients treated for 6 weeks, all reached undetectable virus by follow-up week two, but four of those patients later relapsed, giving an 86.7% SVR at week eight, he reported in his poster presentation and at a press briefing at the annual meeting of the American Association for the Study of Liver Diseases.

“This is a phase II study. This is a proof of principle that we can accomplish SVR at 8 weeks,” Lawitz told MedPage Today. “This was the first time there was a planned 4-week duration trial. Even though there were a number of relapses, it is biologically plausible to cure a very select subset of patients at 4 weeks.”

The researchers conducting the C-SWIFT trial also looked at 6-week and 8-week courses of treatment for harder-to-cure cirrhotic genotype 1 hepatitis C virus-infected patients. “Cirrhotics had SVR of about 95% at 8 weeks,” Lawitz said. He noted that all 102 patients in the study — cirrhotics and noncirrhotics — achieved undetectable virus by follow-up week two. Among the cirrhotic patients, four patients out of 20 who were treated for 6 weeks relapsed. There was one relapse among the 21 cirrhotic patients treated for 8 weeks.

“There are some valuable lessons learned from this,” Lawitz said. “It is encouraging to see a three-drug regimen achieve a 95% SVR at 8 weeks in the setting of cirrhosis. It shows we may be able to get to an 8-week regimen for all patient types.

“Our study looks at short duration therapy,” Lawitz said. The registration trial for the two investigative agents will show SVR12 results. “In the C-SWIFT trial, which is ongoing, we used a three-drug regimen of grazoprevir and elbasvir — the investigative drugs — and sofosbuvir, which is already on the market.

“What we saw at the end of 4 weeks was that all but six patients had achieved undetectable virus, but by follow-up week two those six patients went on to be undetectable, so at follow-up week two there was 100% of patients that were undetectable. In the 6-week arm, all but one patient was negative at the end of the treatment and that patient also went on to become negative by follow-up week two. In the cirrhotic arms all patients were undetectable at either 6 or 8 weeks,” he said.

Lawitz said the three-drug regimen was well-tolerated with few serious adverse events occurring in any treatment regimen, possibly a factor of the short treatment duration.

In commenting on the research, press conference moderator Michael Fried, MD, director of the University of North Carolina Liver Center, Chapel Hill, told MedPage Today, “I agree that this is a very important study because it does sort of set the limits of where we might be able to go with these drugs in terms of duration of therapy.

“Everyone is sort of focused on shorter duration of therapy, and perhaps we can identify certain subgroups that may be able to get treated for 4 weeks, but it certainly will require a lot more research in that area.”

The patients in the C-SWIFT study were in their 50s and more than 60% of each arm of the trial were men. More than 75% of the patients were diagnosed with genotype 1a. Lawitz said the overall study also includes patients diagnosed with genotype 3 hepatitis C virus infection, but the results from that group will be reported at a later meeting.

Reposted from MedPage Today on January 10, 2015:

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Sean Hendrickson