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Ravidasvir/Sofosbuvir Yields Quick SVRs in Largest Genotype 4 Trial
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High Virologic Response Rate in Egyptian HCV-Genotype 4 Patients Treated with Ravidasvir (PPI-668) and Sofosbuvir: Results of a Large Multicenter Phase 3 Registrational Trial.....http://www.natap.org/2015/AASLD/AASLD_54.htm
WEBCAST: http://www.croiwebcasts.org/console/player/29746?mediaType=audio&
Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
In the largest interferon-free trial of HCV genotype 4 patients so far, ravidasvir plus sofosbuvir (with or without ribavirin) yielded high 12-week sustained virologic response rates (SVR12) regardless of interferon treatment experience or cirrhosis [1].
Genotype 4 HCV causes about 15% of chronic HCV infections worldwide but accounts for more than 90% of HCV cases in Egypt. The Pyramid 1 study, a phase 3 registrational trial, compared two regimens in 300 people with genotype 4 HCV: ravidasvir (200 mg once daily) plus sofosbuvir (400 mg once daily) with or without weight-based ribavirin. Ravidasvir is an investigational pangenotypic NS5A inhibitor [2]. The NS5B inhibitor sofosbuvir has not been widely studied for genotype 4 HCV.
Participants had to be between 18 and 65 years old with an HCV load above 10,000 IU/mL but negative for HIV and hepatitis B surface antigen. They could have treatment experience and/or cirrhosis but could not have hepatic decompensation. The four treatment groups were (1a) 90 interferon-naive people without cirrhosis, (2) 80 interferon-experienced people without cirrhosis, (1b) 60 interferon-naive people with cirrhosis, and (3) 70 interferon-experienced people with cirrhosis. Groups 1a, 1b, and 2 all took their regimen for 12 weeks, while group 3 received treatment for 12 or 16 weeks.
Overall age averaged 47.8 years, 68% of participants were men, and pretreatment HCV load averaged 742,180 IU/mL. By treatment week 4, 94% of participants had undetectable HCV RNA, and all patients had undetectable virus by week 8.
Among treatment-naive people without cirrhosis, 100% taking ravidasvir/sofosbuvir (RDV/SOF) and 98% taking RDV/SOF plus ribavirin attained SVR12 in intention-to-treat analyses Among interferon-experienced people without cirrhosis, SVR12 rates were 95% with RDV/SOF and 100% with RDV/SOF plus ribavirin. Nobody without cirrhosis had a treatment relapse.
Among interferon-naive people with cirrhosis, SVR12 rates were 93% with RDV/SOF and 92% with RDV/SOF plus ribavirin in intention-to-treat analyses. In interferon-experienced people with cirrhosis treated for 12 weeks, SVR12 stood at 86%. In interferon-experienced people with cirrhosis treated for 16 weeks, SVR12 was 100% (no relapses or discontinuations). Combining treatment groups and interferon-naive/experienced groups in a per-protocol analysis, the researchers calculated 100% SVR12 in people without cirrhosis and 95% SVR12 with cirrhosis.
Few adverse events arose during the study, with no clear differences between groups with versus without cirrhosis or with versus without interferon experience. Adverse events considered possibly related to study drugs were headache (3%), dosing error (1%), declining hemoglobin (1%), and pruritus (1%). The researchers noted only one serious adverse event possibly related to treatment--a transient episode of symptomatic bradycardia in a patient with cirrhosis, which resolved. Rare symptomatic bradycardia has been reported with sofosbuvir [3].
Pyramid 1 investigators proposed that RDV/SOF could be an attractive once-daily regimen for people with HCV genotype 4 infection.
References
1. Esmat G, El Raziky M, Gomaa A, et al. High response rate in HCV-genotype 4 patients treated with ravidasvir and sofosbuvir. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 153.
2. ChemSpider. Ravidasvir hydrochloride. http://www.chemspider.com/Chemical-Structure.34448417.html
3. Fontaine H, Lazarus A, Pol S, et al. Bradyarrhythmias associated with sofosbuvir treatment. N Engl J Med. 2015;373:1886-1888. http://www.nejm.org/doi/full/10.1056/NEJMc1505967
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