Twelve-week, interferon-free regimen effectively treated chronic HCV

BOSTON — Treatment-naive and previously nonresponsive patients with chronic hepatitis C experienced high rates of sustained virologic response on a regimen of three direct-acting antivirals and ribavirin, according to data presented at The Liver Meeting.

Researchers assigned a daily dose of either 100 mg or 200 mg protease inhibitor ABT-450 (Abbott, Enanta) with 100 mg ritonavir to 571 noncirrhotic patients with chronic HCV, along with either or both 25 mg NS5A inhibitor ABT-267 once daily and/or 400 mg non-nucleoside NS5B inhibitor ABT-333 twice daily, along with or without weight-based ribavirin, for 8, 12 or 24 weeks. All participants were treatment-naive (n=438) or had been unresponsive to previous therapy with pegylated interferon and ribavirin (n=133). The primary endpoint for this ongoing study is sustained virologic response (SVR) at 24 weeks; investigators presented SVR12 data from the 8- and 12-week groups (n=448 patients total) at the meeting.

“ABT-450, ritonavir-containing, interferon-free combinations have previously achieved SVR rates greater than 90% in genotype 1-infected patients in exploratory studies,” researcher Kris V. Kowdley, MD, Virginia Mason Medical Center in Seattle, said. “The goal was to identify optimal interferon-free, direct-acting antiviral combinations in genotype 1-infected patients.”

Among evaluable participants who received all three agents and ribavirin for 12 weeks, SVR12 occurred in 99% of treatment-naive patients and 93% of null-responders, resulting in this regimen being selected for further study. No treatment regimen or duration resulted in an SVR rate less than 89%.

Relapses were more common among patients who received 8 weeks of treatment compared with 12 weeks. Among those who received three agents and ribavirin, relapse occurred in one treatment-naive patient and no null responders, with three participants experiencing virologic breakthrough.

Nearly all patients with HCV genotype 1b achieved SVR12. In the group that received all three agents and ribavirin, 98% of evaluable treatment-naive patients and 89% of null responders with genotype 1a achieved SVR12. Investigators noted that variations to the IL28B gene did not appear to significantly impact SVR12 results.

The drug was well-tolerated across the cohort, with four patients discontinuing therapy because of adverse events. Five serious events occurred, including one incident of arthralgia considered potentially related to the treatment. Fatigue, headache, nausea and insomnia were the most commonly reported events.

“The 12-week, three [direct-acting antivirals] and ribavirin regimen showed the greatest efficacy in both treatment-naive and null-responder populations,” Kowdley said. “The ITT SVR results of 96% in genotype 1a infected, treatment-naive and 89% of 1a-infected null responders are encouraging and warrant further study … the combination of ABT-450 with ritonavir, ABT-267 and ABT-333 will be studied, both with and without ribavirin, in planned phase 3 trials.”

Disclosure: The researchers report numerous financial disclosures.

For more information:

Kowdley KV. LB-1: A 12-Week Interferon-free Treatment Regimen with ABT-450/r, ABT-267, ABT333 and Ribavirin Achieves SVR12 Rates (Observed Data) of 99% in Treatment-Naïve Patients and 93% in Prior Null Responders with HCV Genotype 1 Infection. Presented at: The Liver Meeting 2012; Nov. 9-13, Boston.