- Category: Experimental HCV Drugs
- Published on Tuesday, 29 April 2014 00:00
- Written by Liz Highleyman
A 24-week regimen of sofosbuvir (Sovaldi) plus ribavirin cured 93% of people with hard-to-treat hepatitis C virus (HCV) genotype 4, though treatment for only 12 weeks was not as effective, according to a poster presentation at the EASL International Liver Congress this month in London.
Genotype 4 -- the predominant type in Egypt and several other countries in Africa and the Middle East -- accounts for approximately 20% of HCV infections worldwide and is becoming more common among newly diagnosed people in Europe. Like genotype 1, genotype 4 has traditionally been considered difficult-to-treat compared to genotypes 2 and 3. Most direct-acting antiviral agents (DAAs) have only been tested in small numbers of genotype 4 patients and some have shown minimal activity against this genotype.
Peter Ruane from Ruane Medical and Clinical Research Institute in Los Angeles and colleagues evaluated an interferon-free dual regimen combining the nucleotide HCV polymerase inhibitor sofosbuvir plus ribavirin for HCV genotype 4 patients.
The NEUTRINO study previously showed that sofosbuvir plus pegylated interferon and ribavirin produced a cure rate of 96% for the 28 treatment-naive participants with HCV genotype 4. Sofosbuvir plus ribavirin without pegylated interferon for 12 weeks cures almost all patients with HCV genotype 2, but the VALENCE trial showed that 24 weeks works better for genotype 3. This dual regimen cures a substantial proportion of easier-to-treat genotype 1 patients, but sofosbuvir works better for genotype 1 when combined with another DAA such as ledipasvir.
This single-center Phase 2b trial included 60 patients born in Egypt but living in the U.S. About 70% were men and the mean age was 54 years. Just under half were treatment-naive, most of whom were deemed ineligible to use interferon. The rest had previously been treated with interferon-based therapy, including relapsers, non-responders, and those who stopped due to interferon intolerance. Most (about 80%) had unfavorable IL28B non-CC gene variants, nearly one-quarter had compensated liver cirrhosis, and about 40% had previously had schistosomiasis (a parasitic infection that can cause liver damage).
Participants in this open-label study were randomly assigned to receive 400 mg once-daily sofosbuvir plus 1000-1200 mg/day weight-based ribavirin for either 12 or 24 weeks. The primary endpoint was sustained virological response or undetectable HCV RNA at 12 weeks after finishing treatment (SVR12), considered to be a cure.
- All participants completed treatment.
- SVR12 rates were 68% in the 12-week treatment arm and 93% in the 24-week arm.
- Among treatment-naive participants, the 12- and 24-week SVR12 rates were 70% and 100%.
- Among treatment-experienced patients, SVR12 rates were 59% and 87%, respectively.
- Among treatment-naive patients treated for 12 weeks, people with cirrhosis had a lower SVR12 rate than non-cirrhotics (33% vs 91%), but responses were similar in the other treatment arms.
- IL28B non-CC status was also associated with poorer response in the 12-week arms.
- All virological failures were due to post-treatment relapse, and there were no cases of viral breakthrough while on therapy.
- The S282T sofosbuvir resistance mutation was not detected at baseline or in any patients who experienced treatment failure.
- Sofosbuvir plus ribavirin was generally safe and well-tolerated.
- There were 3 serious adverse events in the 24-week arm; 1 person in this group discontinued ribavirin early due to an adverse event and continued on sofosbuvir monotherapy.
- The most common side effects were headache, insomnia, and fatigue.
- No participants developed severe anemia, though 4 people (14%) in the 24-week arm had mild anemia (hemoglobin <10 g/dL).
"Sofosbuvir + ribavirin provides a simple, interferon-free regimen for patients with HCV genotype 4," the researchers concluded. "Treatment-naive patients had higher SVR12 rates following treatment for 12 or 24 weeks than did treatment-experienced patients. Extending treatment duration to 24 weeks increased SVR rates, particularly for treatment-experienced patients."
PJ Ruane, D Ain, R Meshrekey, et al. Sofosbuvir plus ribavirin, an interferon-free regimen, in the treatment of treatment-naive and treatment-experienced patients with chronic genotype 4 HCV infection. 49th European Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P1243.