The pace of research for HCV is incredible. Two months ago phase 2 data for Sofosbuvir were reported and noted on this blog (More options for Hepatitis C | gutsandgrowth). Now phase 3 data from multiple trials have emerged indicating the effectiveness of sofosbuvir for all HCV genotypes.
In the first study, NEJM 2013; 368: 1867-77, data from two trials (POSITRON and FUSION) of patients with HCV genotypes 2 and 3 are reported. The POSITRON trial (63 sites, n=278 received treatment) was a blinded placebo-controlled study that evaluated 12 weeks of sofosbuvir/ribavirin compared with placebo in patients who discontinued interferon due to unacceptable adverse events or could not take interferon due to contraindications (most commonly psychiatric disorder or autoimmunity). Results: sustained virological response (SVR) in 78% of treatment group compared with 0% of placebo patients. In addition, there was “complete concordance (100%) between rates of SVR at 12 weeks and at 24 weeks.”
The FUSION study (67 sites, n=201 received treatment) was a blinded, active-control study in patients who did not respond to a previous interferon-based regimen; one of two treatment regimens were administered: 12 weeks of sofosbuvir/ribavirin followed by placebo or 16 weeks of sofosbuvir/ribavirin. Results: 93% of genotype 2 patients had SVR and 61% of genotype 3 patients had SVR. Among cirrhotic patients, 61% had SVR (94% of genotype 2, 21% of genotype 3); for those without cirrhosis, there was an 81% SVR (92% with genotype 2, 68% with genotype 3). Thus, it is easy to conclude that genotype 3 patients with cirrhosis responded much less favorably.
Other important findings: rates of discontinuation among the treatment groups were similar to the placebo groups. The most common adverse effect was anemia in the treatment groups.
In the second study, NEJM 2013; 368: 1878-87, an additional two phase 2 trials (NEUTRINO and FISSION) are reported from previously untreated chronic HCV patients. The first trial (NEUTRINO) was an open-label study examining a 12-week regimen of sofosbuvir, peginterferon alfa-2a, and ribavirin in 327 HCV patients (98% genotypes 1 or 4). Results: SVR noted in 90%. The second trial (FISSION) enrolled 499 patients with genotypes 2 and 3 who randomly received either peginterferon alfa-2a/ribavirin for 24 weeks or sofosbuvir/ribavirin for 12 weeks. Results: SVR noted to be 67% in both groups. Genotype 2 patients again fared better than genotype 3 among the sofosbuvir/ribavirin group (97% versus 56%). Some adverse events like fatigue, headache and nausea were common. Overall, side effects were much lower in those not receiving peginterferon (see Table 3).
Take home message: From the editorial (pg 1931-32 in same issue): “a radical change in clinical practice is imminent…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.”
Hopefully, we will see pediatric studies soon.
Related blog entries:
gutsandgrowth 
Pingback: Emerging Targets for Hepatitis C -Part 1 | gutsandgrowth
Pingback: Better HCV Treatments Approved | gutsandgrowth