HCV Combo Overcomes Cirrhosis, Tx Failure
Published: Nov 12, 2014
BOSTON -- Hepatitis C (HCV) patients with cirrhosis are tough to treat. And those who have previously failed therapy are especially difficult.
But 24 weeks of treatment with a newly approved drug combination, sofosbuvir and ledipasvir (Harvoni), cured 97% of patients in a double-blinded, controlled trial, according to Marc Bourliere, MD, of the Saint Joseph hospital in Marseilles, France.
And adding a third drug -- the relatively inexpensive, nonspecific antiviral ribavirin -- allowed investigators to get similar outcomes with just 12 weeks of therapy, Bourliere reported in a late-breaker session at the American Association for the Study of Liver Diseases annual meeting.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
The study was the "most compelling" of the six late-breaker presentations, commented Keith Lindor, MD, of Arizona State University in Phoenix, who was not part of the research but who co-moderated the session.
"The biggest issue for many of us treating these patients is the cost," Lindor toldMedPage Today.
What the study showed, he said, was that adding ribavirin allowed the researchers to avoid 12 extra weeks of treatment with the more expensive direct-acting combination.
"The cost implications are pretty substantial," he said, especially since the efficacy and safety in a difficult-to-treat group of patients was excellent. The combination is being marketed at $1,125 a pill, for a 12-week cost of $94,500.
Bourliere and colleagues enrolled 155 patients with cirrhosis and randomly assigned them to one of two treatment arms.
In the first, patients were given sofosbuvir and ledipasvir for 24 weeks plus a ribavirin placebo. The other arm began with 12 weeks of a placebo for all three drugs, followed by 12 weeks of the combination plus ribavirin.
The initial placebo period was to allow a safety comparison between sofosbuvir/ledipasvir and no treatment.
The patients were highly treatment-experienced; Bourliere told MedPage Today after his presentation that all of them had failed at least two previous attempts at an HCV cure, using older drugs.
The primary endpoint of the study was unquantifiable HCV RNA in the blood 12 weeks after the end of therapy (SVR12).
One patient in the ribavirin arm dropped out owing to an adverse event during the placebo period, and one patient initially randomized to the ribavirin arm was treated with sofosbuvir/ledipasvir for 24 weeks, leaving 77 patients in each arm.
Outcomes were almost identical, Bourliere reported: 74 of 77 patients in the 12-week ribavirin arm and 75 of 77 patients in the 24-week arm achieved SVR12 96% and 97%, respectively.
Four of the five patients who relapsed had been nonresponders to previous therapy, and the fifth suffered a viral breakthrough while on an earlier regimen.
About one in six patients had baseline viral mutations associated with resistance to NSS5A inhibitors, such as ledipasvir, but that had no effect on the chance of achieving an SVR12, Bourliere and colleagues found.
Adverse events were common -- between 87% and 96% of patients reported at least one -- but most were mild, Bourliere said. Only one serious adverse event, a case of anemia in the ribavirin arm, was attributed to treatment.
The only adverse events that were greater in the placebo arm than in the sofosbuvir/ledipasvir arm were headache and fatigue, the researchers found.
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