Studies find high response rates against HCV genotypes without interferon

By Gene Emery

NEW YORK (Reuters Health) - Doctors reported high success rates Sunday in treating different genotypes of the hepatitis C virus using varying combinations of drugs that don't carry the side effects of interferon.

The new results were released during the Digestive Disease Week 2014 meeting in Chicago and online by the New England Journal of Medicine.

About 184 million people have HCV worldwide. It causes more than 350,000 liver disease deaths annually. In some countries, the infection rate can be as high as 5%.

Current therapy carries a high risk of significant side effects, such as flu-like symptoms, neuropsychiatric problems and cytopenias.

Two studies known as PEARL-III and PEARL-IV looked at previously-untreated people with genotypes 1a and 1b, which are responsible for the vast majority of HCV infections. Genotype 1a is most common in North America and is believed to be harder to cure because it is more likely to develop resistance. Genome 1b is particularly common in Europe and East Asia.

Both studies looked at drug combinations with and without ribavirin, which is administered based on body weight. All of the volunteers were otherwise treated with daily doses of 150 mg of the protease inhibitor ABT-450, 100 mg of ritonavir and 25 mg of ombitasvir, all combined into one pill, plus 250 mg of dasabuvir twice a day. The patients were evaluated after 12 weeks of treatment.

In the 305 people with genotype 1a, 97.0% responded with the addition of ribavirin (95% confidence interval 93.7 to 100) compared to 90.2% of those who did not receive it (95% confidence interval 86.2 to 94.3). The rate of virologic failure was just 2.0% with ribavirin and 7.8% without.

Among the 419 patients carrying genotype 1b, the presence of ribavirin made little difference. The sustained virologic response rate was 99.5% with the extra drug (95% confidence interval 98.6 to 100) and 99.0% without (95% confidence interval 97.7 to 100). Only one patient had virologic failure, and that patient was receiving the ribavirin regimen.

Twelve patients suffered serious adverse events. In the genotype 1a study, three patients were receiving ribavirin and one was not. In the genotype 1b study, the eight patients were evenly split between the two groups.

The most common side effects were headache, seen in 23% to 28% of patients, and fatigue, reported by 21% to 46%, with the incidence higher in the genotype 1a group. Nausea, insomnia and pruritus tended to be higher among patients receiving ribavirin as part of their therapy.

Ribavirin also significantly suppressed hemoglobin levels in roughly half the patients.

As a result, some people with blood problems, along with those with heart, lung and kidney disease, might be better off without ribavirin therapy, said the team, led by Dr. Peter Ferenci of the Medical University of Vienna, Austria.

"Given the known teratogenicity of ribavirin, a ribavirin-free regiment would also be preferable for some women of childbearing potential," the researchers say.

Their results come a week and a half after release of the SAPPHIRE I and II trials, which examined the same regimen -- with ribavirin -- in genotype 1 patients, some of whom had not received any previous treatment with an interferon regimen.

They found a sustained virologic response in 96% of volunteers, including those for whom previous treatments had failed to keep the virus at bay. The typical rate with interferon therapy is 78% or lower. That study, as with the new genotype 1 study released Sunday, was financed by AbbVie.

Results from another study released Sunday showed that the combination of sofosbuvir and ribavirin produced a sustained virologic response after 12 weeks of therapy in 93% of 73 patients with a hepatitis C virus genotype 2 infection (95% confidence interval 85 to 98), and in 85% of 250 patients with HCV genotype 3 disease treated for 24 weeks (95% confidence interval 80 to 89).

Those two genotypes account for about 30% of chronic HCV infections.

Fifty eight percent of the patients had previously been treated with interferon. All were originally supposed to receive 12 weeks of treatment with the drug combination or placebo, but the rules for patients with genotype 3 infection were changed in mid-study to provide 24 weeks of therapy and to eliminate the placebo group.

"Patients receiving sofosbuvir-ribavirin had substantial reductions in circulating HCV RNA levels during the first weeks of treatment," said the team, led by Dr. Stefan Zeuzem of the Johann Wolfgang Goethe University Medical Center in Frankfurt, Germany. "By week 4 of treatment, 99% of the patients had an HCV RNA level of less than 25 IU/mL. No patients in the placebo group had an HCV RNA level of less than 25 IU/mL at any time point."

That study is called VALENCE. Gilead Sciences paid for the research.

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N Engl J Med 2014