Two posters exhibited Saturday, November 6, at the 62nd Annual Meeting for the american Association for the Study of Liver Diseases (AASLD) in San Francisco, reported that two new direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV) showed very potent activity against the virus.
The first drug, MK-5172, a second-generation NS3 protease inhibitor from Merck Sharpe & Dohme, was administered in several doses, by itself (monotherapy), for seven days. MK-5172 was designed to have activity against strains of HCV that are resistant to the first-generation HCV protease inhibitors and against multiple HCV genotypes. In the study, researchers gave doses ranging from 50 milligrams (mg) to 800mg once daily to 40 men with HCV genotype 1, and doses ranging from 100mg to 800mg in 24 men with HCV genotype 3. In both groups, the drug was compared with placebo.
Anti-HCV activity was quite high. In those with genotype 1, MK-5172 lowered HCV levels by up to 5.39 logs in those taking the 200mg dose. In those with genotype 3, the 600mg dose lowered HCV levels by 5.22 logs. When researchers looked at the percentage of people whose HCV levels became undetectable after only 7 days of dosing, 75% of those with genotype 1 and 38% of those with genotype 3 reached undetectable.
The most common adverse experienced reported were headache, fatigue, nausea, diarrhea and itchiness. There was a trend toward an increase in a liver enzyme called bilirubin.
The second drug, INX-08189 from Inhibitex, is a different type of DAA than the recently approved drugs Incivek and Victrelis, and MK-5172. It is a nucleotide polymerase inhibitor, which should also have activity against HCV that has become resistant to the first generation of protease inhibitors.
In all, 80 people with HCV genotype 1 were studied on a variety of once-daily doses of INX-08189 or a placebo for seven days. In some of the dosing schemes, INX-08189 or the placebo was combined with ribavirin.
INX-08189 was quite potent against HCV at the highest dose. HCV levels dropped by 4.25 logs by day 8 in those taking the 200mg dose. Drops in HCV in the lower doses did not exceed 2.54 logs. There were also significant drops in alanine aminotransferase (ALT), a key liver enzyme, in those taking the higher doses of the drug.
There were no serious adverse experiences in those taking INX-08189. Milder adverse events included nausea, abdominal pain, diarrhea and nasal congestion.