Shorter Course of Ledipasvir-Sofosbuvir Therapy Effective in Patients with Genotype 1 Hepatitis C

“This comparative analysis was conducted to determine whether it is feasible to shorten the duration of treatment of previously untreated patients with HCV genotype 1 infection with ledipasvir-sofosbuvir from 12 weeks to 8 weeks in the real-world clinical setting,” said Kris Kowdley, MD, of the Swedish Medical Center in Seattle, Washington, at a presentation at Digestive Disease Week 2016, a joint meeting of the American Academy for the Study of Liver Diseases (AASLD), American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

In the real-world clinical setting, it can be useful to shorten therapy. The decision to shorten therapy is usually based on the patient’s treatment history, cirrhosis status, and baseline viral load.

The phase 3 ION-3 trial was a multicenter, randomized, open-label trial consisting of three treatment arms: ledipasvir-sofosbuvir for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary efficacy end point, sustained virologic response, was defined as an HCV-RNA level of less than 25 IU per milliliter at 12 weeks, after the end of therapy. In the ION-3 trial, patients received a fixed-dose combination tablet containing 90 mg of ledipasvir and 400 mg of sofosbuvir, administered orally once daily. Weight-based ribavirin was administered orally twice daily.

In this comparative analysis, data from the ION-3 trial were compared with real-word effectiveness data from six diverse and heterogeneous real-world and post-marketing population cohorts.

While the optimal duration of therapy depends on many factors, post-hoc analyses of the ION-3 clinical trial data with a fixed-dose combination of ledipasvir and sofosbuvir, two direct-acting antiviral agents with distinct viral targets and mechanisms of action, showed that the rapidity and durability of viral suppression achieved with this regimen allows a shorter treatment course of 8 weeks. In this study, the best predictor of sustained virologic response (SVR) was a viral load less than 6 million.

Overall, a total of 123 treatment-naïve, non-cirrhotic patients with a viral load less than 6 million were identified in a post-hoc analysis of the ION-3 clinical trial data. Mean patient age was 52 years, 22% of patients were black, and 72% of patients were genotype 1a. For these patients, the SVR was 97% (119/123). In the real-world population, the overall SVR was also 97% (638/658). No significant impact was observed on the basis of HCV genotypes or subtypes, prior treatment history, presence or absence of cirrhosis, high viral load, or HIV/HCV co-infection.

In this comparative analysis, the real-world effectiveness data yielded SVR response rates that were consistent with those of the phase 3 ION-3 clinical trial data. Given that the SVR rates at 8 weeks were high for treatment-naïve, non-cirrhotic genotype 1 patients with a baseline HCV less than 6 million and possibly in other populations, including HIV/HCV coinfected patients, the data support the use of 8 weeks of ledipasvir/sofosbuvir for this patient population.

“It is also important to note that discontinuation rates were low, despite the diversity of the patient population and the clinical settings,” said Kowdley. These data are also supported by the data from the TARGET and TRIO cohorts, which also suggest that the 8-week treatment regimen is underutilized. “Together, these data suggest that greater use of this shorter treatment course should be encouraged,” he concluded.