www.hivandhepatitis.com

AASLD 2015: New AbbVie Pangenotypic Regimen Cures 97%-100% of Hepatitis C Patients in Early Study

A combination of 2 experimental direct-acting antivirals developed by AbbVie cured 97% to 100% of non-cirrhotic people with genotype 1 hepatitis C in a mid-stage Phase 2 study presented this week at the AASLD Liver Meeting in San Francisco.

[Produced in collaboration with Aidsmap.com]

The SURVEYOR-1 study assessed the effectiveness and safety of 2 next-generation direct-acting antivirals. ABT-493 is an HCV NS3/4A protease inhibitor active against all genotypes of hepatitis C virus (HCV). ABT-530 is a NS5A inhibitor also active against all HCV genotypes. Both agents are active against common viral 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 Sciences (GS-9451), while ABT-530 has demonstrated higher potency than most other NS5A inhibitors across all genotypes.

The new experimental combination is not only active across all genotypes, but does not need ritonavir boosting to maintain adequate levels of its protease inhibitor component. This minimizes the potential for drug-drug interactions, which are a concern with any ritonavir-containing treatment due to the agent’s interaction with a wide range of medications metabolized through the p450 CYP3A4 liver enzyme pathway.

SURVEYOR-1 compared 2 doses of ABT-530 (40 mg or 120 mg) combined with 200 mg of ABT-493, both dosed orally once-daily, for 12 weeks.

The study recruited 79 previously untreated people or prior null responders to pegylated interferon and ribavirin, all with HVC genotype 1 and no evidence of liver cirrhosis. Participants were randomly assigned to the ABT-530 40 mg (n=39) or 120 mg arm (n=40).

Participants were evenly matched in most respects, with an average age of 53 years, 64% previously untreated, and median baseline HCV viral load of 6.6 log IU/mL. Those in the 120 mg arm were more likely to have stage F3 fibrosis (32% vs 18%) and somewhat more likely to be male (58% vs 46%) and to have harder-to-treat genotype 1a (85% vs 77%).

After 12 weeks of treatment, 97% of people in the 40 mg arm and 100% in the 120 mg arm had a sustained virological response 12 weeks post-treatment (SVR12), commonly defined as a cure. One participant experienced viral relapse after completion of treatment in the 40 mg arm. This patient showed no evidence of non-adherence nor baseline resistance mutations that might have contributed to treatment failure, but had 2 NS5A resistance mutations conferring high-level resistance to ABT-530 at relapse. All treatment-experienced patients achieved SVR12.

Treatment was well-tolerated in the vast majority of participants. One grade 3 severe adverse event was reported in the 40 mg arm (metastatic prostate cancer), but this was not considered to be related to treatment. In addition, 2 severe adverse events occurred in the 120 mg arm. One case of elevated blood glucose in a man weighing 115 kg was not considered to be related to treatment, but a case of decreased blood phosphorus was considered study drug-related; however, in all 3 cases the participants achieved SVR 12.

In a subsequent phase of the SURVEYOR-1 study, 34 participants with HCV genotype 1 received 8 weeks of treatment with ABT-530 (120 mg) combined with 200 mg of ABT-493.

Study participants were 56% male, 71% had genotype 1a, and 15% had F3 fibrosis. 88% were previously untreated while 12% were null responders to prior treatment with pegylated interferon and ribavirin.

At 12 weeks post-treatment, 97% of participants (33 of 34) achieved a sustained virological response. One participant discontinued the study at treatment week 4 due to adenocarcinoma, considered unrelated to study drugs. No drug-related serious adverse events were reported. The most frequent adverse event (>5% of patients) was fatigue.

On the basis of these results, AbbVie will test 8- and 12-week regimens in 6 Phase 3 studies due to start this month, using a 120 mg dose of ABT-530 and 200 mg of ABT-493. 

11/17/15

References

F Poordad, F Felizarta, A Asatryan, et al. 98%-100% SVR4 in HCV Genotype 1 Non-Cirrhotic Treatment-Naïve or Pegylated Interferon/Ribavirin Null Responders With the Combination of the Next Gener- ation NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor ABT-530 (SURVEYOR-1). AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract 41.

F Poordad, F Felizarta, A Asatryan, et a. 100% SVR4 in HCV Genotype 1 Non-Cirrhotic Treatment-Naive or -Experienced Patients With the Combination of ABT-493 and ABT-530 for 8 Weeks (SURVEYOR-1). AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract LB-14.

Other Source

AbbVie. AbbVie Announces High Sustained Virologic Response Rates in Phase 2 Studies with Pan-Genotypic, Investigational Regimen in Patients with Chronic Hepatitis C. Press release. November 16, 2015.