Tuesday, April 28, 2015

EASL2015-Sofosbuvir Plus Ribavirin Provides High SVR at 12 Weeks in HCV Genotypes 2 and 3

Sofosbuvir Plus Ribavirin Provides High Sustained Virological Response at 12 Weeks in Patients With Hepatitis C Virus Genotypes 2 and 3: Presented at EASL

By Chris Berrie

VIENNA, Austria -- April 27, 2015 -- Combinations of sofosbuvir plus ribavirin with and without pegylated-interferon alpha-2a (PEG-interferon) are well tolerated and provide high sustained virological response at 12 weeks (SVR12) in patients with hepatitis C virus (HCV) genotypes 2 and 3, according to results of an open-label, phase 3 study presented at the International Liver Congress, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL).

Currently available interferon-free therapies provide relatively low SVR rates for patients with HCV genotype 3. Treatment combinations with sofosbuvir, ribavirin, and PEG-interferon, however, have more recently achieved SVR rates from 68% to 94% for HCV genotypes 2 and 3.

To investigate these options further, investigators for the BOSON study included treatment-experienced HCV genotype 2 with cirrhosis, and HCV genotype 3. “We enriched [the study] for genotype 3 cirrhosis and PEG-interferon/ribavirin failure,” explained lead investigator Graham Foster, PhD, Blizard Institute of Cell and Molecular Science, Queen Mary’s University of London, London, United Kingdom, speaking here on April 25.

Target patients were randomised to 1 of 3 arms: sofosbuvir plus ribavirin for 16 weeks (n = 196) or 24 (n = 199) weeks, or the same combination with PEG-interferon for 12 weeks (n = 197). All patients received sofosbuvir 400 mg daily and ribavirin 1000 to 1200 mg in a divided daily dose, with PEG-interferon administered by injection at 180 µg weekly.

The primary endpoint was SVR12 as HCV RNA <15 IU/mL (lower limit of quantification)

Overall, the SVR12 results for these 16-, 24-, and 12-week treatments were high, with significant benefits for the longer sofosbuvir plus ribavirin regime (72% vs 85%; P = .0013), which provided further significant improvement when combined with PEG-interferon in the shorter treatment regime (85% vs 93%; P = .023).

This finding was paralleled in the HCV genotype 3 data, specifically: 71% versus 84% (P < .001) and 84% versus 93% (P = .008). For the lower numbers of patients with HCV genotype 2, SVR12 was generally higher, with no significant differences: 87% versus 100% versus 94%, respectively.

Further analysing patients with HCV genotype 3, SVR12 was generally higher in patients without cirrhosis across the treatment groups (80% vs 87% vs 95%) than in those with cirrhosis (51% vs 79% vs 88%), and for treatment-naïve patients (77% vs 88% vs 95%) than for treatment-experienced patients (64% vs 80% vs 91%).

This finding was paralleled within the cohort of treatment-naïve patients without cirrhosis (83% vs 90% vs 96%) and with cirrhosis (57% vs 82% vs 91%), and within the cohort of treatment-experienced patients without cirrhosis (76% vs 82% vs 94%) and with cirrhosis (47% vs 77% vs 86%).

The safety analysis demonstrated similar levels of adverse events across the treatment groups (94% vs 95% vs 99%), with no specific safety worries for grade 3/4 adverse events (6% vs 4% vs 8%) or serious adverse events (4% vs 5% vs 6%).

In the laboratory analyses, there were increased rates of grade 3/4 adverse events with the addition of PEG-interferon (15% vs 15% vs 38%), as well as increased haemoglobin <10 g/dL (4% vs 6% vs 12%), and platelets <50,000/mm3 (<1% vs 0% vs 5%).

While all treatment regimens with all of these patient populations were well tolerated, with low rates of treatment discontinuation due to adverse events, Dr. Foster noted, “It seems that interferon may still have a role to play in some particular populations.”

Patient baseline characteristics in this study were well balanced across the treatment arms, with the full cohort showing a mean age of 50 years, 67% male, and a mean HCV RNA 6.3 log10 IU/mL. In all, 92% of patients had genotype 3, and the enrichment group included 37% patients with cirrhosis and 53% treatment-experienced patients.

Funding for this study was provided by Gilead Sciences, Foster City, California.

[Presentation title: Sofosbuvir Plus PEG-IFN/RBV for 12 Weeks vs Sofobuvir/RBV for 16 or 24 Weeks in Genotype 3 HCV-Infected Patients and Treatment-Experienced Cirrhotic Patients with Genotype 2 HCV: the BOSON Study. Abstract L05]

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