New Antiviral Drug Regimen Highly Effective Against Hep C

Results of two recent clinical trials suggest a new antiviral drug regimen could be highly effective in eradicating the hepatitis C virus—even in patients with liver scarring and at risk of cancer or transplant. The findings appear online in JAMA.

The drug combination also worked in patients with chronic hepatitis C infection without liver cirrhosis. The direct-acting antivirals were designed to combat the genotype 1 virus, the most common hepatitis C infection in the United States.
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“The combination of daclatasvir, asunaprevir, and beclabuvir was successful in achieving high cure rates in both cirrhotic and noncirrhotic genotype 1 patients in the UNITY-1 and UNITY-2 studies,” says investigator and study co-author Fred Poordad, MD, of the University of Texas Health Science Center in San Antonio. “This supports that using direct-acting antiviral agents that target different proteins is a successful way to eradicate virus in most patients.”

The UNITY-1 trial included patients with chronic hepatitis C virus genotype 1 infection without cirrhosis, while the UNITY-2 trial evaluated patients with hepatitis C virus genotype 1 infection and compensated cirrhosis.

In both trials, the drug combination achieved eradication rates of about 90% and more based on a measure called sustained virologic response, which meant there was an undetectable level of virus genetic material in the patients’ blood serum samples sustained for 12 weeks.

The authors suggest these findings may be a step forward in identifying effective and well tolerated, interferon-free regimens to treat patients with chronic hepatitis C virus infection and cirrhosis.

“The concept of combining drugs with different mechanisms of action is the best way to minimize failure through resistance, and also has been shown to be highly effective in treating the hepatitis C virus,” Poordad says. “The landscape continues to brighten with every new regimen that is introduced, suggesting that in a few years, novel combinations using direct-acting antiviral agents may offer the highest chance of cure, with the least chance of adverse events or resistance.”

Based on the outcomes, the regimen he and his colleagues tested has been shown to be safe and well tolerated and the doses used were appropriate. “Further testing of various components of this regimen—in particular, daclatasvir—are ongoing, even in combination with other agents,” Poordad says.

Currently, the US Food and Drug Administration is reviewing a daclatasvir-based regimen for patients with genotype 3 hepatitis C virus.

“The submission is based on data from phase 3 ALLY program, which evaluates the regimen in multiple high-unmet need patient populations,” Poordad says. “We anticipate the current FDA review of the regimen for genotype 3 patients will be followed in later months with the submission of data for other difficult-to-treat patient populations.”

—Colleen Mullarkey

References

1. Poordad F, Sievert W, Mollison L, Bennett M, Tse E, Bräu N, et al. Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection. JAMA. 2015;313(17):1728-35.

2. Muir AJ, Poordad F, Lalezari J, Everson G, Dore GJ, Herring R, et al. Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis. JAMA. 2015;313(17):1736-44.