番茄社区

BOSTON -- Eight weeks of hepatitis C (HCV) treatment with a novel three-drug combination was not as good as an older combination of two drugs delivered for 12 weeks, a researcher reported here.

In a large randomized trial, the 8-week regimen of sofosbuvir/velpatasvir (Epclusa) plus the investigational drug voxilaprevir was not non-inferior to 12 weeks of sofosbuvir/velpatasavir, according to , of Mount Sinai Hospital in New York City, and colleagues.

The three drugs delivered an overall cure rate of 95% in patients with all six HCV genotypes, with or without cirrhosis, but that did not match the 98% rate delivered by the older combination, Jacobson reported in a late-breaker session here at the

The relative lack of efficacy was driven by a high relapse rate among patients with viral genotype 1a -- two-thirds of all the relapses seen among patients treated with the three drugs, Jacobson reported.

In other genotypes, the outcomes were comparable between the two combinations, he added.

For that reason, it might be too early to write off the 8-week regimen entirely, commented , of the University of Colorado in Denver, who was not involved in the study but who co-moderated the session at which it was presented.

"They did show that 8 weeks versus 12 weeks was successful in a large percentage of patients," Sokol told 番茄社区, adding that "moving towards 8 weeks [of treatment] is still a big advance."

Although the now direct-acting agents against HCV are much safer and more tolerable than older interferon-based therapy, they are expensive, he noted. A shorter treatment course would make therapy easier for patients and clinicians alike.

"I don't know what the final interpretation of the data is going to look like," Sokol said, noting that late-breaking abstracts have -- almost by definition -- not been completely analyzed. It might be, he added, that investigators and regulators will conclude that 8-week treatment is the way to go for almost all patients, with those harboring genotype 1a virus getting an extra month of the drugs.

The sofosbuvir/velpatasavir combination, given for 12 weeks, is highly effective in previously untreated patients with all HCV genotypes, Jacobson said. But Phase II studies had suggested that adding the NS3/4A protease inhibitor voxilaprevir would allow equivalent efficacy with a shorter treatment course.

To test the idea, the team enrolled 941 patients who had not been previously treated with direct-acting agents and randomly assigned them to one of the combinations. Both combinations were co-formulated into a single pill to be taken once daily.

The primary endpoint of the study was the proportion of patients reaching a sustained virologic response 12 weeks after the end of treatment -- the so-called SVR₁₂ -- which was defined as HCV RNA below the lower limit of quantification at that point.

SVR₁₂ is regarded as a cure because very few patients relapse after they achieve it.

To compare the two arms of the study, the investigators set a statistical benchmark: the combinations would be regarded as non-inferior if the lower bound of 95% confidence interval for the difference in SVR₁₂ rates was greater than -5%.

The patient population was well balanced between the arms, although only a handful of patients had the rarer genotypes 5 and 6. About 50% of patients in each arm had genotype 1, with about three-quarters of those having genotype 1a.

Both combinations were safe and well tolerated, Jacobson said -- only four patients stopped therapy, including two because of adverse events and one lost to follow-up in the sofosbuvir/velpatasavir arm. The only dropout in the triple-drug arm was a woman who became pregnant.

But the bottom line was that investigators saw 21 relapses (after the end of therapy and before SVR₁₂) in the triple-drug arm and just three in the other group, he reported. Because of that, the difference in SVR₁₂ rates was high enough that the triple-drug combination did not reach non-inferiority.

But, 16 of those relapses were among patients with genotype 1, and 14 were among patients with genotype 1a. In comparison, only one relapse occurred in each group when treated with sofosbuvir/velpatasavir.

In other genotypes, relapse numbers were comparable, as were SVR₁₂ rates.

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