Boston—Can treatment of hepatitis C infection with new direct-acting antivirals (DAAs) be shortened to less than 12 weeks? Interim results from a recent trial suggest treatment durations of eight or even four weeks may be possible with the right combination of drugs.
Shortened regimens would help contain health care costs, with 12-week courses of new DAAs hovering close to $100,000. Prolonged treatment may also compromise patient adherence to therapy, experts said.
“Optimized regimens may allow an eight-week duration that may be broadly applicable across diverse patient groups,” said Eric Lawitz, MD, vice president of scientific and research development at The Texas Liver Institute, in San Antonio, who led the study. Dr. Lawitz, also clinical professor of medicine at the San Antonio University of Texas Health Science Center, said large randomized trials are needed before changes to clinical practice can be made.
In the new study, presented at the 2014 Liver Meeting of the American Association for the Study of Liver Diseases (abstract LB33), Dr. Lawitz and his colleagues hypothesized that a regimen of DAAs that target different components of the replication cycle of the hepatitis C virus (HCV) would allow for a shorter duration of therapy than what is currently used—12 to 24 weeks for most patients. The Phase II C-SWIFT trial tested four, six or eight weeks of sofosbuvir (Sovaldi, Gilead), an NS5B nucleotide polymerase inhibitor, plus Merck’s fixed-dose combination of grazoprevir, an NS3/4A protease inhibitor, and elbasvir, an NS5A inhibitor.
The study enrolled treatment-naive patients with HCV genotypes 1 and 3, but only results from genotype 1 patients were presented at the meeting. At two weeks of follow-up after the end of treatment, no patient in any of the treatment arms had detectable levels of virus. However, only patients who received eight weeks of therapy had sustained virologic responses (SVRs) similar to those seen with the 12-week regimens currently used (Table).
The shortened regimen was well tolerated, according to the researchers. Patients relapsed most commonly with either wild-type virus or with resistance-associated amino acid variants already present at baseline. Factors associated with the likelihood of achieving an SVR in the arms that received only four or six weeks of treatment were subgenotype, viral load at baseline, IL28Bstatus and the pharmacokinetics of component medicines in the regimen.
Dr. Lawitz reported that 12 of 31 patients receiving four weeks of treatment were cured of HCV.
“Although there were a number of patients that relapsed, I think it is important that it is biologically plausible to cure a very selected subset of patients at four weeks,” Dr. Lawitz said. “The study teaches us what the phenotype might be for patients who have an opportunity to be successful with a shorter duration of therapy.”
Dr. Lawitz added that he hoped the findings will be used to design future trials to test shorter durations of therapy.
“It is also encouraging to see that a three-drug regimen achieved a 95% SVR at eight weeks in the setting of cirrhosis,” Dr. Lawitz said, pointing out that many currently approved regimens are approved for 24 weeks in cirrhotic patients. “This suggests that we may be able to feasibly get an eight-week regimen for all patient types. Obviously we need large, prospective studies to evaluate the question, but it is a proof of principle.”
The interim results from the Phase II trial will be updated later with SVR12 data.
Michael Fried, MD, director of the University of North Carolina Liver Center, at Chapel Hill, said researchers were focused on shortening the treatment time of patients with hepatitis C.
“This is a very important study because it sets the limits, if you will, of where we might be able to go with these drugs,” Dr. Fried said. “Perhaps we can identify certain subgroups of patients that would be able to get treated for four weeks, but that will certainly require a lot more research.”