HealthDay News — The investigational drug sofosbuvir appears to be quick acting and effective against chronic hepatitis C virus (HCV) infection, results from two reports suggest.
Although focused on different patient populations, both show sofosbuvir, a novel oral nucleotide analogue, can achieve high cure rates with an acceptable safety profile in just 12 weeks, researchers reported in New England Journal of Medicine. The results were also presented this week at the Internal Liver Congress in Amsterdam.
In comparison, time to cure for the current standards of care, pegylated interferon and ribavirin, is 48 weeks.
In an accompanying NEJM editorial, Joost P.H. Drenth, MD, PhD, of Radboud University Nijmegen Medical Center in Nijmegen, the Netherlands, said the findings suggest “a radical change in clinical practice is imminent.”
Sofosbuvir is different from previous HCV medications in that it works directly against the virus, and may enable healthcare providers to phase out interferons, a therapy well known for it’s extensive side effects.
The two most recent additions to the HCV treatment arsenal, the protease inhibitors telaprevir and boceprevir, must be administered with peginterferon and ribavirin and have been found to further aggravate associated side effects.
This has made routine management of adverse events associated with HCV treatment an ongoing challenge of care. “Physicians and patients are ready for less toxic therapeutic options,” Drenth wrote.
In the first phase III trial, NEUTRINO, Edward Gane, MD, of Auckland City Hospital in Auckland, New Zealand, and colleagues investigated sofosbuvir in 327 patients mainly with HCV genotype 1, and several patients with genotypes 4, 5 and 6.
Patients were treated with sofosbuvir plus pegylated interferon and ribavirin for 12 weeks in a single-arm, open-label study. The primary endpoint was sustained virologic response (SVR), defined as viral loads too low to quantify,12 weeks after the end of therapy.
The researchers found that 90% of patients achieved SVR at 12 weeks, compared with an adjusted historical response rate of 60%.
Furthermore, there with no significant differences in response rates by HCV genotype. Among the 291 patients with HCV genotype 1, 89% achieved SVR at 12 weeks, as did 96% of the 28 genotype 4 patients. All six patients with genotype 6, and the single genotype 5 patient also reached the primary endpoint.
Gane and colleagues also conducted a second phase III study, FISSION, to assess noninferiority of two weeks of oral therapy with sofosbuvir and ribavirin in 499 patients with HCV genotypes 2 and 3 vs. the current standard of care of pegylated interferon, given intravenously, and ribavirin for 24 weeks.
SVR at 12 weeks was identical for both groups at 67%, showing that the all-oral sofosbuvir regimen was noninferior to standard of care.
In both studies, the most common adverse events were fatigue, headache, nausea and insomnia.
In two other studies, published in a separate NEJM report, Ira Jacobson, MD, of Weill Cornell Medical College in New York City, and colleagues assessed sofosbuvirs efficacy and safety in patients with HCV genotypes 2 and 3 who were treatment naive or nonresponders to standard treatment.
The POSITRON study involved 278 patients for whom treatment with peginterferon was not an option, because of other health issues such as psychiatric or autoimmune disorders.
Patients were randomly assigned 3:1 to treatment with either oral sofosbuvir and ribavirin, or placebo for 12 weeks. SVR was 78% among those treated with sofosbuvir and ribavirin vs. 0% in the placebo group (P<0.001), the researchers found.
The FUSION study involved 201 patients who had not responded to previous therapy with interferon and ribavirin and were randomly assigned to receive sofosbuvir and ribavirin for either 12 or 16 weeks.
At 12 weeks, 50% of patients achieved SVR vs. 73% among those treated for 16 weeks (P<0.001).
Common side effects in these two studies were similar to those observed by Gane et al, and included headache, fatigue, nausea and insomnia.
“The low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drugs are strong selling points of a sofosbuvir–ribavirin regimen and will probably lower the threshold for HCV treatment for both patients and physicians,” Drenth wrote.
However, he acknowledged “a note of caution is appropriate,” as other side effects may become apparent with wider use of sofosbuvir and as longer term data become available.
- Lawitz E et al. “Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection.” N Engl J Med. 2013; doi: 10.1056/NEJMoa1214853.
- Jacobson IM et al. “Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options.” N Engl J Med. 2013; doi: 10.1056/NEJMoa1214854.
- Drenth JP. “HCV Treatment — No More Room for Interferonologists?” N Engl J Med. 2013; doi: 10.1056/NEJMe1303818.