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C-WORTHy: Novel therapies show promise in patients with cirrhosis, previous null responders
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LONDON — Response rates to combination therapy with two novel Merck compounds with or without ribavirin were higher than 90% across a cohort of traditionally difficult-to-treat patients with hepatitis C virus, according to new data presented here.
Eric Lawitz, MD, from the Texas Liver Institute and University of Texas Health Science Center, reported data from the C-WORTHy study. The researchers assessed the efficacy, safety and effective treatment duration of the NS3/4A protease inhibitor MK-5172 in combination with NS5A replication complex inhibitor MK-8742 (both Merck) with or without ribavirin. The analysis included treatment-naive patients with HCV genotype 1 infection who had cirrhosis and/or had a prior null response to pegylated interferon and ribavirin.
MK-5172 was administered at 100 mg daily with MK-8742 at 50 mg daily with or without weight-based ribavirin for 12 or 18 weeks.
Eric Lawitz
The COBAS TaqMan v2.0 was used to measure treatment response. The researchers defined the lower limit of quantitation as <25 IU/mL. The analysis included 123 treatment-naïve cirrhotics. In this arm, 63 patients received ribavirin and 60 received no ribavirin. Among 130 null responders, 65 received ribavirin and 65 received no ribavirin.
Response rates at week 4 in the treatment-naive groups ranged from 90% to 100%. By week 8 of follow-up, the response rates also exceeded 90%. In null responders with and without cirrhosis, efficacy rates ranged from 94% to 100%.
In the arm of the study that included patients treated for 18 weeks, follow-up at week 4 revealed efficacy rates above 90%. The efficacy rate among patients with genotype 1a infection, regardless of treatment, was 94%. For those with genotype 1b infection, the efficacy rate was 99%. There were nine virologic failures, or 3.6% of the study population, according to Lawitz. In addition, seven serious adverse events were distributed across the four arms, he said during a presentation. “Three patients discontinued due to adverse events. There was no anemia in the ribavirin-free arm.”
Two percent of patients experienced elevations of ALT or AST above the upper limit of normal, according to Lawitz, who noted that these incidents were ultimately improved or resolved. Fatigue, headache and asthenia were the most commonly reported adverse events.
“Overall, 90% to 97% of cirrhotics have shown SVR4 or SVR8,” Lawitz said. “Also, 91% to 100% of prior null responders achieved SVR4/SVR8.” – by Rob Volansky
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Disclosure: Lawitz reports receiving research support from AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Idenix Pharmaceuticals, Janssen, Merck, Novartis, Presidio, Roche, Santaris Pharmaceuticals and Vertex Pharmaceuticals, and serving on speakers’ bureaus for Gilead, Janssen, Kadmon, Merck and Vertex Pharmaceuticals.