Ravidasvir plus sofosbuvir demonstrates high cure rate for people with hepatitis C genotype 4

Imam Waked presenting at CROI 2016. Photo by Liz Highleyman, hivandhepatitis.com

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 month in Boston.

Direct-acting antiviral agents used in interferon-free regimens have revolutionised 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 of 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 people with genotype 4 hepatitis C. Ravidasvir, formerly known as PPI-668, is being co-developed by Pharco Pharmaceuticals in Egypt and Presidio Pharmaceuticals in San Francisco.

Glossary

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

naïve

In HIV, an individual who is ‘treatment naïve’ has never taken anti-HIV treatment before.

treatment-naïve

A person who has never taken treatment for a condition.

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 US, Europe and Asia, and has not been as extensively studied as genotype 1.

Pyramid 1 enrolled 300 people with genotype 4 chronic hepatitis C 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 200mg ravidasvir and 400mg sofosbuvir, both taken 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.

Among participants without cirrhosis treated with ravidasvir and sofosbuvir alone, 100% of previously untreated and 95% of treatment-experienced participants 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 participants with cirrhosis, SVR12 rates were 93% with ravidasvir and sofosbuvir alone and 92% with the addition of ribavirin. Among the treatment-experienced participants with cirrhosis, only 86% were cured with 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 group with cirrhosis, treated for 12 weeks (including one participant 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 one serious adverse event, bradycardia (slow heartbeat), considered to be probably related to study drugs; this participant 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 diarrhoea (2%). Three people taking ribavirin developed anaemia and two 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 people with cirrhosis, the researchers concluded. Adding ribavirin did not improve response rates for people without cirrhosis or previously untreated patients.

References

Esmat G et al. (Waked I presenting) High response rate in HCV-genotype 4 patients treated with ravidasvir and sofosbuvir. Conference on Retroviruses and Opportunistic Infections (CROI), Boston, abstract 153, 2016.

View the abstract on the conference website.

View a webcast of this session on the conference website.