ABT-493 + ABT-530 cures most hepatitis C patients across genotypes in SURVEYOR studies

A co-formulation of AbbVie's experimental next-generation direct-acting antiviral agents ABT-493 and ABT-530 was well-tolerated and led to sustained virological response in 97% or more of patients across all hepatitis C virus (HCV) genotypes in a set of studies reported last week at the Digestive Disease Week (DDW) 2016 meeting in San Diego.

Interferon-free therapy using direct-acting antivirals has revolutionised treatment for chronic hepatitis C, but researchers continue to try to optimise therapy, especially for difficult-to-treat patients such as those with liver cirrhosis or hard-to-treat HCV genotype 3. An ideal regimen would not require ribavirin and would be pangenotypic, or active against multiple HCV genotypes.

The phase 2b SURVEYOR trials evaluated a pangenotypic combination of the HCV NS3/4A protease inhibitor ABT-493 plus the NS5A inhibitor ABT-530. The studies had multiple parts and included various patient populations based on HCV genotype, prior treatment experience and presence of liver cirrhosis.

SURVEYOR-1 initially enrolled chronic hepatitis C patients with HCV genotype 1 and no cirrhosis. They were treated with ABT-493 (200 or 300mg) plus ABT-530 (40 or 120mg) once-daily for 12 weeks. The second part of the study evaluated a shorter 8-week treatment duration for genotype 1 patients without cirrhosis, and a 12-week duration for genotype 1 patients with cirrhosis and people with genotypes 4, 5 and 6 without cirrhosis.

SURVEYOR-2 recruited patients without cirrhosis with HCV genotype 2, and genotype 3 patients with or without cirrhosis, both treatment-naive and prior non-responders. They were treated with ABT-493 and ABT-530 once-daily for 8 or 12 weeks; one of the 12-week arms included ribavirin.

Prior results from SURVEYOR-1 and SURVEYOR-2 were presented at the AASLD Liver Meeting this past November. Researchers at DDW reported pooled results from these studies according to HCV genotype.

Fred Poordad of the Texas Liver Institute presented results for genotype 1 and 2 patients without cirrhosis treated with 300mg ABT-493 + 120mg ABT-530 for 8 weeks.

In the group of 34 genotype 1 patients 56% were men, the median age was 54 years, 71% had harder-to-treat HCV subtype 1a, 15% were treatment-experienced and 12% had advanced fibrosis (stage F3). Of the 54 genotype 2 patients 61% were men, the median age was 57 years, 13% were treatment-experienced and 6% had stage F3 fibrosis. NS3 or NS5A resistance-associated substitutions were detected in 76% and 58%, respectively, at baseline.

Overall, 97% of genotype 1 patients and 98% of genotype 2 patients achieved sustained virological response, or continued undetectable HCV viral load at 12 weeks post-treatment (SVR12). One genotype 1 patient discontinued early due to a non-drug-related adverse event and a genotype 2 patient was lost to follow-up. In a modified analysis that excluded these non-virological failures, the cure rates were 100% for both genotype groups.

Treatment was generally safe and well tolerated, with one non-drug-related serious adverse event in each genotype group. The most commonly reported adverse events were fatigue and headache, mostly mild. No grade 2 or higher laboratory abnormalities were observed.

The combination of ABT-493 and ABT-530 for 8 weeks led to high SVR12 rates "regardless of baseline viral load, prior treatment history or HCV subtype," the researchers concluded.

Andrew Muir of Duke University School of Medicine reported findings for treatment-naive genotype 3 patients without cirrhosis in SURVEYOR-2 who were treated with 300mg ABT-493 + 120mg ABT-530 for 8 weeks.

In Part 1 of this study, 97% of patients treated with this regimen for 12 weeks were cured in a modified analysis, setting the stage for testing of the shorter duration.

This analysis included 29 patients. Half were men, the median age was 47 years, 86% had HCV subtype 3a and a quarter had stage F3 fibrosis. 46% had NS3 or NS5A resistant variants at baseline.

The overall SVR12 rate was 97%. One patient withdrew consent after treatment in week 6, leaving a cure rate of 100% when excluding this non-virological failure. Again treatment was well tolerated, with no serious adverse events, grade 3-4 laboratory abnormalities or discontinuations due to adverse events.

Finally, Edward Gane of Auckland City Hospital in New Zealand presented results from part 2 of SURVEYOR-1, looking at patients without cirrhosis with HCV genotypes 4, 5 or 6 who were treated with 300mg ABT-493 + 120mg ABT-530 for 12 weeks.

Although HCV genotype 1 is most common in Europe, North and South America and much of Asia, genotypes 4, 5 and 6 occur more often in low- and middle-income countries with a high burden of hepatitis C. Genotype 4 is the predominant type in the Middle East and parts of Africa, genotype 5 is most common in South Africa and genotype 6 is found in parts of Asia.

This analysis included 34 patients: 22 with genotype 4, 1 with genotype 5 and 11 with genotype 6. Half were men, a quarter were Asian, the median age was 55 years, 15% were treatment-experienced and 15% had advanced fibrosis.

The SVR12 rate was 100% for all these less extensively studied genotypes. Treatment was safe and well tolerated, with no serious adverse events, grade 2 or higher laboratory abnormalities, or discontinuations for this reason.

Based on these findings from SURVEYOR-1 and SURVEYOR-2, phase 3 studies are now evaluating ABT-493 plus ABT-530 for 8 or 12 weeks in a larger number of patients with all six major HCV genotypes, with and without cirrhosis.