Simple, Short HCV Regimen Has High Cure Rate – MedPage Today

Meeting Coverage

Published: Apr 12, 2014

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LONDON — A single pill once a day for 8 weeks is enough to cure more than 90% of hepatitis C virus (HCV) patients with relatively uncomplicated disease, a researcher said.

In a large phase III open-label trial, 94% of patients with HCV genotype 1 and no cirrhosis were able to clear the virus after just 8 weeks of sofosbuvir (Sovaldi) and ledipasvir co-formulated in a single once-daily pill, according to Kris Kowdley, MD, of Virginia Mason Medical Center in Seattle.

Neither a longer duration of treatment nor the addition of the antiviral drug ribavirin had any effect on the combination’s efficacy, Kowdley reported here at the annual meeting of the European Association for the Study of the Liver and online in the New England Journal of Medicine.

The fixed-dose combination was “safe and well tolerated” with adverse events more common among patients treated with ribavirin, Kowdley told a crowded plenary session of the meeting.

The outcome is “pretty dramatic,” commented Adrian Di Bisceglie, MD, of St. Louis University School of Medicine in St. Louis, Mo., who was not part of the study but who moderated the plenary session at which it was presented.

“You’re talking about one pill once a day for 8 weeks,” he told MedPage Today, a stark contrast to the “year of torture” involved in treating the disease only a few years ago.

Whether regimens can go even shorter remains up in the air. Kowdley said a 4-week regimen would be the “holy grail” for clinicians — because it would mean a single prescription — but that so far has eluded researchers.

Di Bisceglie said most people getting the combination were negative for the virus by 4 weeks: “How much consolidation beyond that does one need?”

But even 8 weeks, he said “makes this very manageable for patients.”

Sofosbuvir, approved last year, is one of the so-called direct-acting agents against HCV; it’s a nucleotide analog NS5B polymerase inhibitor that targets part of viral replication process. Ledipasvir, which blocks the action of the viral nonstructural protein 5A, remains under investigation, but the drugs have been put together as a single pill.

The so-called ION-3 trial is one of several phase III studies here reporting how the fixed-dose combination of the two drugs worked in different patient populations.

ION-3, Kowdley said, enrolled 647 previously untreated patients and randomly assigned them to get ledipasvir-sofosbuvir for 8 weeks, the combination plus ribavirin also for 8 weeks, or the two drugs alone for 12 weeks.

The primary endpoint was sustained virologic response at 12 weeks after the end of therapy, or SVR₁₂, defined as a lack of detectable HCV RNA at that point. The SVR₁₂ is regarded as tantamount to a cure because few patients relapse after they have achieved that milestone.

Kowdley and colleagues found that the SVR₁₂ rate was:

• 94% with 8 weeks of ledipasvir-sofosbuvir alone
• 93% if ribavirin was added for 8 weeks
• 95% with 12 weeks of ledipasvir-sofosbuvir alone

The minimal differences suggested that the 8-week ledipasvir-sofosbuvir regimen had efficacy that was noninferior to either of the other two, Kowdley said.

In each of the three arms, he said, response rates were high and similar based on subgroups defined by such things as sex, race, HCV sub-genotype, and baseline HCV viral load.

The proportion of patients reporting adverse events was numerically higher in the ribavirin-containing arm, he reported, as were grade 3 and 4 lab abnormalities. As expected, hemoglobin declines were more common among the patients getting ribavirin.

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