A course of new antiviral drugs in a clinical trial has resulted in almost all the patients with chronic hepatitis C infection becoming virus-free, even those whose disease meant they had scarring of the liver and so were at transplant or cancer risk.
The results of the two trials of the drugs used in combination – daclatasvir, asunaprevir and beclabuvir – are published online by JAMA.
The trials, one including people with liver disease, the other without, both saw eradication rates of around 90% and more against a measure of aviremia called sustained virologic response (SVR).
This meant there was an undetectable level of virus genetic material in blood serum samples, defined as having HCV RNA below the level of virus detection at 25 international units per milliliter (IU/mL), sustained for 12 weeks.
In the study of people with severe liver scarring but stable hepatic function, a condition known as compensated cirrhosis – so not advanced to cancer or other severe disease known as decompensated cirrhosis – 202 patients were treated twice-daily with an all-oral antiviral combination of daclatasvir (30 mg), asunaprevir (200 mg) and beclabuvir (75 mg).
Viral elimination – as measured by SVR at week 12, “SVR12” – was achieved for up to 98% of patients. This highest rate was for those receiving ribavirin added in with the trio combination; the rate was 93% otherwise.
Lower rates were achieved by these treatments in patients who had already tried other established therapies before the trial, three quarters of whom had failed to respond to interferon-based regimens.
These treatment-experienced groups still achieved SVR12 rates of 87% for patients receiving the drug combo alone and 93% for patients with ribavirin added.
Overall, the authors conclude, SVR12 was achieved by 93% of 202 patients with genotype 1 infection and compensated cirrhosis after 12 weeks of treatment with the fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir, with or without Ribavirin.
In outlining what they suggest is the importance of the development, the authors summarize: “Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus infection and cirrhosis.”
Dr. Hari Conjeevaram, of the University of Michigan in Ann Arbor, writes in an accompanying editorial:
“These two studies add to the armamentarium of all-oral interferon-free regimens that have revolutionized management of hepatitis C, not only for patients who are treatment-naïve with no significant liver disease but also for those who are treatment-experienced and those with cirrhosis.”
The hepatitis C virus infects liver cells – the resulting severe inflammation of the organ can cause long-term complications.
The World Health Organization (WHO) state that about 60% of people infected, whether with symptoms or not, go on to be HCV carriers, with the remaining 40% recovering fully. Of these carriers, an estimated 20% develop scarring of the liver. About a fifth of those with cirrhosis also develop liver cancer.
WHO describes the symptoms, when reported, of hepatitis C infection, saying it can progress to jaundice in about a quarter of patients whose insidious onset involves:
The first author of the study in liver-scarred-patients was Dr. Andrew Muir, of the Duke University Medical Center in Durham, NC. There were three serious adverse events that were considered to be side effects of treatment, with four patients discontinuing therapy after experiencing adverse events. Dr. Muir concludes with coauthors:
“In this open-label, uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12.”
In the trial of the drugs in patients without hepatic cirrhosis, there were seven serious adverse events but they were all thought to be unconnected with the study treatment. One patient died after treatment but this too was not thought to be related to the medication. The adverse events reported in more than 10% of patients were headache, fatigue, diarrhea and nausea.
The trial was conducted by Dr. Fred Poordad, of the University of Texas Health Science Center in San Antonio, and colleagues, and results showed virologic failure in just 8% of patients – there was an overall SVR12 rate of 92% for treatment-naïve patients (379 of 415 patients) and 89% for treatment-experienced patients (92 of 103).
“This study demonstrates that 12 weeks of therapy with the DCV-TRIO regimen without ribavirin was associated with high rates of SVR12 in patients with HCV genotype 1 infection,” the authors conclude.
Both clinical trials were funded by New York City-headquartered pharmaceutical company Bristol-Myers Squibb.