NEJM - Keeping up with Novel Hepatitis C Genotype 1 Trials

Keeping up with Novel Hepatitis C Genotype 1 Trials

This week’s NEJM features two studies (ION-1 and ION-3) that examine ledipasvir, a NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, for previously untreated HCV infection.  A recent search of the New England Journal of Medicine archives for the term “HCV” returned 45 original research articles from the last 5 years. For many of us, the significance of a highly effective regimen that is interferon/ribavirin-free may get lost among the other 45 papers if one does not grasp the long road taken to get to this point...

 Continue reading....

Links
ION-1
New England Journal Of Medicine
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.

ION-3
New England Journal Of Medicine 
Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis 
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.

Abstract @ GastroHep.com
Sustained virological response with ledipasvir–sofosbuvir for previously untreated HCV 

This week's publication of the New England Journal of Medicine evaluates the use of ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis
High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir.

Dr Kris Kowdley and colleagues examined 8 weeks of treatment with this regimen.
In this phase 3, open-label study, the team randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir–sofosbuvir) for 8 weeks, ledipasvir–sofosbuvir plus ribavirin for 8 weeks, or ledipasvir–sofosbuvir for 12 weeks.

The team's primary end point was sustained virologic response at 12 weeks after the end of therapy.
The rate of sustained virologic response was 94% with 8 weeks of ledipasvir–sofosbuvir, 93% with 8 weeks of ledipasvir–sofosbuvir plus ribavirin, and 95% with 12 weeks of ledipasvir–sofosbuvir.

As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir–sofosbuvir, the rate in the 12-week group was 1 percentage point higher, and the rate in the group that received 8 weeks of ledipasvir–sofosbuvir with ribavirin was 1 percentage point lower.

The team report that these results indicated noninferiority of the 8-week ledipasvir–sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points.

The researchers observed that adverse events were more common in the group that received ribavirin than in the other 2 groups.

The team noted that no patient who received 8 weeks of only ledipasvir–sofosbuvir discontinued treatment owing to adverse events.

Dr Kowdley's team concludes, "Ledipasvir–sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis."

"No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks."