DAA Combination Treatment Fast and Effective for Hepatitis C

Two phase 2 studies of combination direct-acting antiviral agent (DAA) treatments were published recently in Gastroenterology. They were accompanied by an editorial simply titled “Hepatitis C Therapy: Game Over!”

The optimism of that title stems from the strength of the results the two studies produced and the variety of hepatitis C (HCV) genotypes they covered. One dealt entirely with genotype 1, while the other examined the treatment’s efficacy in genotypes 2, 3, 4, and 6.

As DAAs have become more and more specific in targeting the virus’s ability to replicate, they have shown the ability to quickly eradicate HCV. Previous trials have shown their safety in combination, and with the increased potency, their ability to destroy the virus in a shorter course of treatment and thus save healthcare costs. The DAAs in question for the two recent studies were sofosbuvir, velpatasvir, and voxilaprevir (Gilead Science's GS-9857), which each inhibit different viral proteins vital to the proliferation of HCV.

The studies examined patients who were either treatment-naïve or treatment-experienced (having failed with previous DAA regimens), and among them, those who suffered cirrhosis and those who did not. Different lengths of treatment with the triple combination were compared, and the endpoint was SVR12, or sustained virologic response 12 weeks after treatment.

In the genotype 1 study, 71% of the treatment-naïve patients without cirrhosis who underwent 6 weeks of treatment achieved SVR12, and 100% of those administered 8 weeks of the treatment did so. Among the treatment-naïve that did have cirrhosis, the number was 94% after 8 weeks. Treatment-experienced patients both with and without cirrhosis all achieved SVR12 after receiving a 12 week course of the combination treatment.

These results were fairly consistent with cohorts in the genotypes 2, 3, 4, and 6 study. All treatment-experienced patients without cirrhosis and all but one (28 of 29) with cirrhosis in that study achieved the endpoint after a 12 week course of treatment. Among treatment-naïve patients, 88% without cirrhosis reached SVR12 after a 6 week treatment and 93% with cirrhosis did so after an 8 week run.

The coinciding editorial, authored by Alessio Aghemo and Maria Buti, lauds the combination’s ability to “shorten treatment duration in treatment naïve patients and provides a valuable option to previous DAA failures” and its “excellent safety profile, being ribavirin free.” The three are combined into a fixed-dose tablet.

The genotype 1 study was led by Eric Lawitz of the Texas Liver Institute, and the genotype 2, 3, 4, and 6 study was led by Edward J. Gane of the New Zealand Liver Transplant Unit at Auckland City Hospital. Their research was funded by Gilead Sciences, maker of the investigational GS-9857. Complete results of phase 3 studies involving the combination will be presented later this month at The Liver Meeting in Boston.

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