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EASL 2016: AbbVie Pangenotypic Combination Achieves High Cure Rate for Genotype 3 Hepatitis C

A new combination of direct-acting antivirals developed by AbbVie -- ABT493 and ABT-530 -- is highly effective in curing people with genotype 3 hepatitis C virus (HCV) infection and liver cirrhosis, according to results from a pair of Phase 2 studies presented at last week’s EASL International Liver Congress (EASL 2016) in Barcelona.

[Produced in collaboration with infohep.org]

Almost 30% of hepatitis C infections worldwide 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 HCV is more difficult to cure than other genotypes, 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 pangenotypic regimen for hepatitis C treatment.

ABT-493 is an HCV NS3/4A protease inhibitor active against all genotypes of HCV. ABT-530 is an NS5A inhibitor, also active against all genotypes. 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 from Merck (grazoprevir) and Gilead (GS-9451). ABT-530 has demonstrated higher potency than most other NS5A inhibitors across all genotypes.

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

SURVEYOR-II enrolled 48 previously untreated people with genotype 3 HCV infection and randomized them to receive either ABT-493 (300 mg) and ABT-530 (120 mg) dosed once daily, or the same regimen with once-daily ribavirin (800 mg), 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 log IU/mL.

The primary endpoint of the study was sustained virological response, or undetectable HCV RNA 12 weeks after post-treatment SVR12. At 12 weeks after the completion of treatment, all participants had 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 (anemia 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.

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 (300 mg) and ABT-530 (120 mg) dosed once daily.

This study also excluded treatment-experienced people or those with HIV and HCV coinfection. 52% of participants were male, 90% were white, and the median HCV RNA was 6.5 log₁₀ IU/ml.

The primary endpoint of the study again was SVR12. At 12 weeks after 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 that time.

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

4/22/16

References

P Kwo, DL Wyles, S Wang, et al. 100% SVR12 with ABT-493 and ABT-530 with or without ribavirin in treatment-naive HCV genotype 3-infected patients with cirrhosis. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract LB01.

AJ Muir, S Strasser, S Wang, P Wo, et al. High SVR rates with ABT-493 + ABT-530 co-administered for 8 weeks in non-cirrhotic patients with HCV genotype 3 infection. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract PS098.

Other Source

AbbVie. AbbVie Presents New Phase 2 Data for Investigational, Once-Daily, Ribavirin-Free, Pan-Genotypic Regimen of ABT-493 and ABT-530 for Hepatitis C Genotypes 1-6. Press release. April 16, 2016.