New AbbVie hepatitis C combination cures 93 to 97% with genotype 3

Paul Kwo, presenting at AASLD 2015. Photo by Liz Highleyman,
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A combination of two experimental direct-acting antivirals developed by AbbVie cured 93 to 97% of people with genotype 3 hepatitis C infection after a 12-week course of treatment, Paul Kwo of Indiana University School of Medicine reported on Monday at the 2015 AASLD Liver Meeting in San Francisco.

Genotype 3 infection is associated with an increased risk of fibrosis progression and liver cancer (hepatocellular carcinoma) compared to other genotypes, making affordable and effective treatment options for this group of patients an important unmet need.

Genotype 3 hepatitis C infection is more difficult to cure than other genotypes of hepatitis C, requiring a longer course of treatment with most regimens. The only currently approved 12-week interferon-free regimen for treatment of genotype 3 consists of daclatasvir (Daklinza) and sofosbuvir (Sovaldi). 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.



Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 


A drug that acts against a virus or viruses.

viral breakthrough

An increase in viral load while on antiretroviral treatment.

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

The SURVEYOR-2 study assessed the effectiveness and safety of two experimental next-generation direct-acting antivirals, with or without ribavirin, at different doses. ABT-493 is an HCV NS3/4A protease inhibitor active against all genotypes of hepatitis C. ABT-530 is a 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.

The SURVEYOR-2 study recruited 120 people with genotype 3 infection, who were randomised to one of four 12-week regimens:

  • ABT-493 (300mg) and ABT-530 (120mg)

  • ABT-493 (200mg) and ABT-530 (120mg)

  • ABT-493 (200mg) and ABT-530 (120mg) and ribavirin

  • ABT-493 (200mg) and ABT-530 (40mg)

All agents were dosed once daily.

The study recruited previously untreated people or previous null responders to pegylated interferon and ribavirin, with no evidence of cirrhosis. There was some variation across study arm in demographic characteristics, notably in the proportion of men (48 to 63%) and F3 fibrosis (10 to 23%). The mean HCV viral load ranged from 6.3 to 6.7 log10/IU/ml across the four study arms.

Twelve weeks after the completion of treatment, rates of sustained virological response (SVR12) ranged from 83% in the ABT-493 (200mg) and ABT-530 (40mg) arm to 93% in the two remaining ribavirin-sparing arms and 94% in the ribavirin-containing arm. In a per-protocol analysis which excluded non-virological failures, sustained virological response rates were highest (97%) in the ABT-493 (300mg) and ABT-530 (120mg) arm and in the ribavirin-containing arm. A single on-treatment viral breakthrough occurred in both the ribavirin arm and the ABT-493 (200mg) and ABT-530 (40mg) arms, leading researchers to conclude that ABT-493 300mg and ABT-530 120mg were most likely to prevent viral breakthrough. This dose will now be taken forward in further studies in patients with cirrhosis and as a shorter, 8-week treatment course in patients without cirrhosis.

The number of treatment-experienced participants in the study was very low due to the exclusion of people who had taken direct-acting antivirals in addition to pegylated interferon and ribavirin, and so it is difficult to draw meaningful conclusions.

Two severe drug-related adverse events were reported: one case of decreased haemoglobin in the ribavirin-containing arm and one increase in creatine phosphokinase (CPK) in the ABT-493 (300mg) and ABT-530 (120mg) arm. Commonly reported side effects were fatigue, headache and nausea, and most adverse events were mild or moderate. Laboratory abnormalities were most frequently reported in the ribavirin group (three cases of grade 2 haemoglobin decrease).

Genotype 2: no virological failures with ABT-493 and ABT-530

The SURVEYOR-2 study also contained a genotype 2 population in which a 12-week treatment course was tested at three different doses:

  • ABT-493 (300mg) and ABT-530 (120mg)

  • ABT-493 (200mg) and ABT-530 (120mg)

  • ABT-493 (200mg) and ABT-530 (120mg) and ribavirin

The study recruited 75 participants, randomised equally between the three arms. Eligibility criteria were the same as for the genotype 3 population.

Sustained virological response rates (SVR12) were very high: 96% in the 300mg/120mg arm, and 100% in the remaining arms, with the less-than-total virological response rate explained by the loss of one participant to follow-up at week 2.

Two participants experienced severe adverse events of headache which may have been study drug-related in the opinion of investigators, but in one case the headaches resolved within two days and in the other case, migraine headaches in a chronic sufferer became less severe and subsided more quickly after ribavirin dose reduction.

A combination of ABT-493 (300mg) and ABT-530 (120mg) will now be taken forward for further studies in genotype 2 populations, including patients with cirrhosis and those who have failed sofosbuvir/ribavirin, and an 8-week treatment course will be tested.


Kwo P et al. SURVEYOR-II: High SVR4 rates achieved with the next generation NS3/4A protease inhibitor ABT-493 and NS5A inhibitor ABT-530 in non-cirrhotic treatment-naïve and treatment-experienced patients with HCV genotype 3 infection. AASLD Liver Meeting, San Francisco, abstract 248, 2015.

Wyles D et al. SURVEYOR-II: High SVR4 rates achieved with the next generation NS3/4A protease inhibitor ABT-493 and NS5A inhibitor ABT-530 in non-cirrhotic treatment-naïve and treatment-experienced patients with HCV genotype 2 infection. AASLD Liver Meeting, San Francisco, abstract 250, 2015.