Neil Canavan

July 11, 2013

KUALA LUMPUR, Malaysia — A new interferon-free drug regimen for the treatment of hepatitis C is safe and effective in treatment-naïve patients and in those who previously had a poor response to treatment, according to the phase 2b AVIATOR trial.

The direct-acting antiviral combination, manufactured by AbbVie Pharmaceuticals, consists of the protease inhibitor ABT-450, the non-nucleoside NS5B polymerase inhibitor ABT-333, and the novel NS5A inhibitor ABT-267. When used in combination with ribavirin, it reportedly produces sustained virologic response rates of up to 99% in patients with hepatitis C.

Barry Bernstein, MD, vice president of infectious disease at AbbVie, and his team evaluated the safety and efficacy of this interferon-free regimen in combination with ribavirin to determine whether toxic events would lead to dose reductions in ribavirin and whether that would have any effect on treatment outcome.

Ribavirin is a key component of effective hepatitis C treatment, but often it cannot be used at optimum therapeutic levels when combined with interferon — the current standard of care.

Dr. Bernstein presented the results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C.

In the AVIATOR trial, first presented last year at the annual meeting of the American Association for the Study of the Liver Diseases, patients were treated with the interferon-free combination with or without ribavirin for 12 or 24 weeks.

In the study cohort, 159 patients were treatment-naïve and 88 were previous nonresponders to ribavirin. Median age was 50 years, and was 86% of the cohort was white. All patients had chronic infection with hepatitis C genotype 1 and plasma HCV RNA levels above 50,000 IU/mL.

The primary end points were safety and sustained virologic response at 24 weeks.

Four patients (1.6%) discontinued treatment because of adverse events, 1 patient experienced a serious adverse event (arthralgia), and 16 patients (6.5%) had hemoglobin levels below 10 g/dL.

In 24 of the 247 (10%) patients, the dose of ribavirin was reduced because of adverse events. Of these, 20 were treatment-naïve and 4 were previous nonresponders.

The incidence of ribavirin dose reductions was similar in the 12- and 24-week treatment groups.

The most common adverse events were anemia, with 10 events reported, and fatigue, with 3 events reported. Other events, with 2 reports each, were diarrhea, dizziness, and pruritus.

There were more adverse events in treatment-naïve patients than in nonresponders.

All 24 patients whose dose of ribavirin was reduced achieved a sustained virologic response at 24 weeks. For those without a dose reduction, 92.1% of the treatment-naïve patients and 94.0% of the nonresponders achieved a sustained virologic response at 24 weeks

"Significantly, ribavirin dose reduction occurred less frequently than in previous studies of peg-interferon-containing regimens," said Dr. Bernstein. As important, he noted, is the fact that when dose reductions did occur, response rates were not negatively affected.

Toward Interferon-free Treatment

Preliminary trials to determine drug–drug interactions with HIV medications are near completion, and a trial of this drug combination in patients coinfected with HIV and hepatitis C will start soon, Dr. Bernstein said.

These results, if they hold up, will be very significant for people coinfected with HIV and hepatitis C, said Tom Campbell, MD, a principal investigator of the Colorado AIDS Clinical Trial Unit. "The exciting thing is that they don't require the use of interferon, which is very poorly tolerated, particularly in people with coinfection."

The need for interferon-free regimens is clear. "We have patients who are waiting for new drugs before they are willing to be treated, particularly those who have less advanced hepatitis C infection who don't need immediate treatment," Dr. Campbell explained. He acknowledged that "it will be a few years before these drugs are approved for HIV and hepatitis C coinfection, so it is a bit of a gamble to wait."

However, he understands the reluctance of these patients to be treated now. "It's a decision that the patient should make in consultation with their care provider."

Dr. Bernstein is an employee of AbbVie Pharmaceuticals. Dr. Campbell has disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TUAB0103. Presented July 2, 2013.


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