AbbVie pan-genotypic combination for hepatitis C achieves 97-100% cure rate in genotype 3

Keith Alcorn
Published:
20 April 2016
Paul Kwo presenting at ILC 2016. Photo by Liz Highleyman, hivandhepatitis.com

A new combination of direct-acting antivirals developed by AbbVie is highly effective in curing hepatitis C in people with genotype 3 infection and cirrhosis, results of two phase II studies presented at last week’s International Liver Congress showed.

Almost 30% of worldwide hepatitis C infections are estimated to be genotype 3, with a particular concentration in the Indian sub-continent and among populations of Indian origin living elsewhere. Genotype 3 is also widespread in the Russian Federation, Scandinavia, Thailand, Brazil and Australia. Genotype 3 hepatitis C virus (HCV) is more difficult to cure than other genotypes of HCV, requiring a longer course of treatment with most regimens. The most effective available regimens for treatment of genotype 3 have cured between 78 and 88% of people treated.

AbbVie is developing the combination of ABT-493 and ABT-530 as a pan-genotypic regimen for hepatitis C treatment.

Glossary

compensated cirrhosis

The earlier stage of cirrhosis, during which the liver is damaged but still able to perform most of its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.

ABT-493 is an HCV NS3/4A protease inhibitor active against all genotypes of hepatitis C. ABT-530 is an NS5A inhibitor also active against all genotypes of HCV. Both agents are active against common variants that confer resistance to first-generation agents of their classes. ABT-493 is more potent against genotype 3 than other HCV protease inhibitors, including products being developed by Merck (grazoprevir) and Gilead (GS-9451), and ABT-530 has demonstrated higher potency than most other NS5A inhibitors across all genotypes.

Dr Paul Kwo of the University of Indiana presented results from the SURVEYOR-II study in people with compensated cirrhosis (Child-Pugh A cirrhosis).

SURVEYOR-II enrolled 48 previously untreated people with genotype 3 infection and randomised them to receive either ABT-493 (300mg) and ABT-530 (120mg) dosed once daily, or the same regimen with once-daily ribavirin (800mg), for 12 weeks.

The study excluded treatment-experienced people, those with a previous history of liver decompensation and people with HIV and HCV co-infection.

The two study arms were evenly matched in most respects, although men predominated in the ribavirin arm (75 vs 52% in the ribavirin-sparing arm) and a higher proportion of the ribavirin-sparing arm had a Child-Pugh score above 6 (21 vs 13%). Median HCV RNA was 6.4 log10 IU/ml.

The primary endpoint of the study was sustained virologic response. Twelve weeks after the completion of treatment all participants had sustained virologic response (SVR12), regardless of baseline resistance profiles (18 participants had viral variants associated with resistance in either the NS3 or NS4A regions, and 4 participants had viral variants associated with resistance in both regions).

Two serious adverse events occurred in the ribavirin arm (anaemia possibly related to ribavirin, and a delusional disorder possibly related to study drugs on the same day as amphetamine and alcohol use). Mild adverse events including headache, fatigue, nausea and dizziness occurred more frequently in the ribavirin arm.

Paul Kwo also presented results of a small study of an 8-week treatment course of the same regimen in people with genotype 3 infection without cirrhosis. A previous dose-ranging study had observed a high cure rate after 12 weeks of treatment in both treatment-experienced and previously untreated patients; this study was designed to test whether an 8-week course of treatment could deliver a similar cure rate (>95%) in patients without cirrhosis.

The study assigned 29 previously untreated patients to receive an 8-week course of treatment with ABT-493 (300mg) and ABT-530 (120mg) dosed once daily. The study excluded treatment-experienced people or those with HIV and HCV co-infection.

Fifty-two per cent of participants were male, 90% were white and the median HCV RNA was 6.5 log10 IU/ml.

The primary endpoint of the study was sustained virologic response. Twelve weeks after the completion of treatment 28 out of 29 participants had achieved SVR12 (97%). One participant withdrew at week 6 due to intolerance of blood draws but had an undetectable HCV RNA at this time.

No serious adverse events occurred during the study and the most common adverse events were headache, fatigue, nausea and diarrhoea. One participant experienced a grade 2 bilirubin elevation (>1.5-3 x ULN).

References

Kwo P et al.100% SVR12 with ABT-493 and ABT-530 with or without ribavirin in treatment-naive HCV genotype 3-infected patients with cirrhosis. International Liver Congress, Barcelona, abstract LB01, 2016.

Muir A et al. High SVR rates with ABT-493 + ABT-530 co-administered for 8 weeks in non-cirrhotic patients with HCV genotype 3 infection. International Liver Congress, Barcelona, 2016.

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