CROI 2013: AbbVie Interferon-free Combos Cure Most Newly Treated Hepatitis C Patients

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All-oral regimens containing the HCV protease inhibitor ABT-450, a non-nucleoside polymerase inhibitor, and ribavirin led to sustained response for more than 90% of previously untreated patients -- including those with unfavorable IL28B gene patterns -- but only about half of prior non-responders, researchers reported at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) last week in Atlanta.

Direct-acting antiviral agents that target various steps of the hepatitis C virus (HCV) lifecycle have brought about a new treatment paradigm for chronic hepatitis C, and many patients and clinicians are eagerly awaiting all-oral regimens without interferon.

Eric Lawitz from the University of Texas Health Science Center and colleagues compared various interferon-free combinations of direct-acting drugs being developed by AbbVie (formerly Abbott).

All 12-week regimens included the once-daily HCV NS3/4A protease inhibitor ABT-450, boosted with ritonavir (Norvir) to achieve adequate levels in the body (ABT-450/r). They also included a non-nucleoside HCV NS5B polymerase inhibitor -- either ABT-072 taken once daily or ABT-333 taken twice daily -- and 1000-1200 mg/day weight-based ribavirin.

Lawitz presented combined data from 4 cohorts in 2 studies:

About 70% of participants overall were men (though this varied from about one-half to 100% in different treatment arms), about 80% were white, and the average age was approximately 53 years. About 80% had more difficult-to-treat HCV subtype 1a. In Cohort 4, about 60% were prior partial responders (still-detectable HCV RNA at the end of previous interferon-based therapy) and the rest null responders (less than a 2-logdecline in HCV RNA). People with HIV and hepatitis B coinfection were excluded.

Enrollment in Cohort 1 was restricted to patients with the favorable IL28B CC gene pattern, which is associated with good interferon response; its role in interferon-free therapy is not yet clear. In Cohort 2 half had the CC pattern, about one-third had the CT (intermediate) pattern and about 10% were TT (least favorable). In Cohort 3 the CC and CT proportions were reversed. In Cohort 4 no one had the CC pattern (typical of non-responders) while about 70% were CT and 30% TT.

Results

"We're in a state of a paradigm shift to the era of direct-acting antivirals," Lawitz said at an accompanying CROI press conference. "For those with mild-to-moderate disease, as timelines for approval [of direct-acting drugs] firm up, we're using interferon less and putting more people in the warehouse" to wait for interferon-free treatment.

3/15/13

References

E Lawitz, D Cohen, F Poordad, et al. 12 Weeks of ABT-450/Ritonavir, Non-nucleoside Inhibitor and Ribavirin Achieved SVR24 in >90% of Treatment-naïve Hepatitis C Virus GT1 Patients and 47% of Prior Non-responders. 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013). Atlanta, March 3-6, 2013. Abstract 38.

M King, W Xie, L Larsen, et al. Risk of Virologic Relapse in Hepatitis C Virus GT1-infected Subjects after 8, 12, and 24 Weeks of ABT-450/r+ABT-267+ABT-333+Ribavirin: Identifying Optimal Treatment Duration, 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013). Atlanta, March 3-6, 2013. Abstract 39.