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CROI 2016: Ravidasvir Plus Sofosbuvir Demonstrates High Cure Rate for HCV Genotype 4

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Sofosbuvir plus the investigational HCV NS5A inhibitor ravidasvir, with or without ribavirin, cured 95% to 100% of people with hepatitis C virus (HCV) genotype 4, the most common type in Egypt, according to findings from the Pyramid 1 study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2016)last week in Boston.

Direct-acting antiviral agents used in interferon-free regimens has revolutionized treatment for chronic hepatitis C, but there is still a need for better therapies for harder-to-treat patients. Ideally treatment would be pan-genotypic, or active against all HCV types, so it could be routinely prescribed in resource-limited settings without the need for genotype testing.

Imam Waked from the National Liver Institute in Egypt reported results from Pyramid 1, a Phase 3 study evaluating Gilead Sciences' HCV NS5B polymerase inhibitor sofosbuvir (Sovaldi) and the pan-genotypic NS5A inhibitor ravidasvir for genotype 4 hepatitis C patients. Ravidasvir, formerly known as PPI-668, is being co-developed by Pharco Pharmaceuticals in Egypt and Presidio Pharmaceuticals in San Francisco.

HCV genotype 4 accounts for 15% of all chronic hepatitis C cases worldwide and is the predominant type throughout the Middle East and parts of Africa, Waked noted as background. More than 90% of Egyptians with hepatitis C have this genotype, but it accounts for a small proportion of cases in the U.S., Europe, and Asia, and has not been as extensively studied as genotype 1.

Pyramid 1 enrolled 300 genotype 4 chronic hepatitis C patients in Egypt. Nearly 70% were men and the mean age was approximately 48 years. Half were previously untreated and half had received prior interferon-based therapy. More than 40% had compensated liver cirrhosis.

Participants were stratified according to prior treatment and cirrhosis status:

  • Group 1a (n=90): treatment-naive without cirrhosis;
  • Group 1b (n=60): treatment-naive with cirrhosis;
  • Group 2 (n=80): treatment-experienced without cirrhosis;
  • Group 3 (n=70): treatment-experienced with cirrhosis.

Participants in groups 1a, 1b, and 2 received 200 mg ravidasvir and 400 mg sofosbuvir, both once-daily for 12 weeks, and were randomly assigned to either add ribavirin or not. The harder-to-treat patients in group 3 received ravidasvir plus sofosbuvir and ribavirin for either 12 or 16 weeks.

Results

  • Among participants without cirrhosis treated with ravidasvir and sofosbuvir alone, 100% of previously untreated and 95% of treatment-experienced patients achieved sustained virological response, or continued undetectable viral load at 12 weeks after completion of treatment (SVR12).
  • Among those who added ribavirin, SVR12 rates were 98% and 100%, respectively.
  • Looking at treatment-naive cirrhotic participants, SVR12 rates were 93% with ravidasvir and sofosbuvir alone and 92% with the addition of ribavirin.
  • Among the treatment-experienced patients with cirrhosis, only 86% were cured ravidasvir, sofosbuvir and ribavirin taken for 12 weeks, but the SVR12 rate rose to 100% when treatment was extended to 16 weeks.
  • No relapses occurred among participants without cirrhosis, and all treatment failures were due to early discontinuation.
  • The highest relapse rate -- 10.5% -- was seen in the treatment-experienced cirrhotic group treated for 12 weeks (including 1 patient who discontinued due to an adverse event after 8 weeks), but there were no relapses with 16-week treatment.
  • Treatment was generally safe and well-tolerated.
  • There was 1 serious adverse event, bradycardia (slow heartbeat), considered to be probably related to study drugs; this patient discontinued treatment at week 8 and the abnormality resolved.
  • The most common adverse events were headache (13%), abdominal discomfort (6%), fatigue (5%), itching (4%), and diarrhea (2%).
  • 3 people taking ribavirin developed anemia and 2 lowered their ribavirin dose.

Ravidasvir plus sofosbuvir with or without ribavirin "shows high sustained response rates" in this largest-ever study of interferon-free therapy for people with genotype 4 HCV, with the highest proportion of patients with cirrhosis, the researchers concluded. Adding ribavirin did not improve response rates for people without cirrhosis or previously untreated patients.

3/4/16

Reference

G Esmat, M El Raziky, A Gomaa, I Waked, et al. High Response Rate in HCV-Genotype 4 Patients Treated With Ravidasvir and Sofosbuvir. Conference on Retroviruses and Opportunistic Infections. Boston, February 22-25, 2016. Abstract 153.