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CROI 2013: Telaprevir Triple Therapy Improves HCV Response for Black Null Responders

Adding the HCV protease inhibitor telaprevir (Incivek) to pegylated interferon and ribavirin increased end-of-treatment response rates for difficult-to-treat patients including African-Americans who previously did not respond to interferon, according to study results presented at the recent 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013)in Atlanta.

The advent of direct-acting antiviral agents has brought about a new paradigm of hepatitis C treatment, especially for patients who do not respond well to standard interferon-based therapy. These include people of African descent and prior null responders who saw little or no decrease in HCV RNA (< 2 log) with previous treatment. Research has shown that the effects of race and prior non-response are largely attributable to unfavorable IL28B gene patterns.

Steven Flamm from Northwestern University and fellow investigators with the OUTLOOK study conducted a Phase 4 (post-marketing) study to evaluate the efficacy and safety of adding telaprevir to pegylated interferon/ribavirin for black and non-black patients with HCV genotype 1 who did not achieve sustained virological response (SVR) with prior treatment.

In this open-label study, participants received 750 mg 3-times-daily telaprevir in combination with 180 mcg/week pegylated interferon and 1000-1200 weight-based ribavirin for 12 weeks.

The CROI presentation included 27 prior null responders -- 20 of them African-American -- who had received at least 12 weeks of triple combination therapy. In the African-American group 55% were men, the mean age was 56 years, 65% had harder-to-treat HCV subtype 1a, 45% had liver cirrhosis, and 90% were found to have the unfavorable IL28B CT or TT gene patterns.

Results 

• 12 of 20 African American prior null responders (60%) achieved undetectable HCV RNA at week 12 of triple therapy.
• 3 of 20 patients discontinued study drugs due to stopping rules for likely futility based on early response at weeks 4-12.
• 2 additional participants discontinued treatment early for other reasons (1 due to side effects, 1 withdrawal of consent).
• Safety and tolerability were similar to that observed in previous Phase 3 trials.
• Adverse events included fatigue (55%), anemia (55%), rash (40%), and pruritus or itching (30%).

"Preliminary data in this hard-to-treat African-American, prior null responder patient population receiving telaprevir combination treatment have displayed encouraging early virologic responses with 60% of patients having undetectable HCV RNA at week 12," the researchers concluded.

"This early virologic response is especially notable because African-American null responders have historically demonstrated lower virologic responses to antiviral therapy," they added. "In addition, hepatitis C is more prevalent among African Americans."

4/10/13

Reference

S Flamm, E Martin, A Muir, et al. Telaprevir Combination Treatment in Hard-to-treat African American, Null Responder G1 Chronic Hepatitis C Patients: Early Data from the OUTLOOK Study. 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013). Atlanta, March 3-6, 2013. Abstract 678.