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by Tracy Swan

It is difficult not to be dazzled by cure rates of up to 100% from interferon-free hepatitis C virus (HCV) trials presented at the American Association for the Study of Liver Diseases (AASLD) meeting in November 2012.

Here we provide a glance at some key interferon-free trials data from AASLD. A comprehensive review of clinical trials data is now available through the TAG/i-Base Pipeline Report web portal:

Genotype 1 Treatment Update

Cure rates in treatment-naive people receiving interferon-free regimens remain impressive, yet HCV subtype (1a vs. 1b) and IL28B genotype (CC vs. non-CC) may impair efficacy of certain regimens. This was the case in a pair of phase II trials: Abbott Laboratories’ AVIATOR (combining ABT-450/r, a ritonavir-boosted protease inhibitor, and ABT-267, an NS5A inhibitor, either with or without ABT-333, a non-nucleoside polymerase inhibitor, or ribavirin) and Boehringer Ingelheim’s SOUND-C2 (combining faldaprevir, a protease inhibitor, and BI 201127, a non-nucleoside polymerase inhibitor, with or without ribavirin).

In contrast, neither HCV subtype nor IL28B genotype had an impact on treatment outcomes in a BMS/Gilead phase II trial combining daclatasvir (an NS5A inhibitor) and sofosbuvir (a nucleotide polymerase inhibitor), or in ELECTRON, which combined sofosbuvir and GS-5885 (an NS5A inhibitor).

AASLD also brought good news for treatment-experienced people with HCV genotype 1, notably null responders (those with minimal response to peginterferon and ribavirin). In AVIATOR, 89% to 93% of null responders maintained undetectable HCV levels for 12 weeks (SVR-12) after completing 12 weeks of all-oral treatment. In Gilead’s ELECTRON, three of three null responders given 12 weeks of sofosbuvir, GS-5885, and ribavirin reached the SVR-12 milestone.

Adding oral drugs to peginterferon and ribavirin also significantly boosted SVR among null responders in Roche’s MATTERHORN trial and BMS’s QUAD trial, AI447-011.

Genotypes 2 and 3

Encouraging results from peginterferon-free trials in treatment-naive and treatment-experienced people with HCV genotypes 2 and 3 were presented at AASLD. But recent results from Gilead’s POSITRON study—issued by press release in late 2012—underscore the importance of larger trials in more “real-life” populations. POSITRON included interferon- ineligible, -intolerant, and -unwilling participants starting treatment for the first time. After 12 weeks of sofosbuvir and ribavirin, SVR was only 61% in genotype 3—no better than with 24 weeks of peginterferon and ribavirin (in treatment- naive people).

Interferon-free regimes offer huge advantages: improved tolerability, safety, and convenience for treatment-naive people with HCV genotypes 2 and 3. Yet high prices will make these drugs unappealing to payers without a clear demonstration of improved efficacy and the potential to fill unmet therapeutic needs.

Although the future of HCV treatment—interferon-free, effective, safe, tolerable, and convenient regimens—holds great promise for people living with hepatitis C, more information is needed about these regimens in people coinfected with HIV; liver transplant candidates and recipients; people with renal impairment; and people with cirrhosis (especially those who are treatment-experienced)—in other words, people with the greatest immediate need of a safe and highly effective cure.

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