Clinical

VX-950 rapidly lowers hepatitis C viral RNA load

Last Updated: 2006-11-21 10:17:26 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Hepatitis C viral (HCV) RNA levels decline within days of initiation of treatment with VX-950 (telapravir), according to a report by Dutch researchers.

"To date in clinical studies that have evaluated VX-950 dosing over a period of 14 or 28 days, either alone or in combination, VX-950 has shown rapid and dramatic antiviral activity in all patients," Dr. Hendrik W. Reesink from Academic Medical Center, Amsterdam, told Reuters Health.

In the October issue of Gastroenterology, Dr. Reesink and colleagues note that they evaluated the safety and tolerability of multiple doses of VX-950, a peptidomimetic of HCV-encoded serine protease NS3-4A, in 34 patients with chronic hepatitis C. They were treated with 450 or 750 mg every 8 hours or 1250 mg every 12 hours.

Median HCV RNA levels fell by 3.46 to 4.77 log10 IU/mL within 3 days of initiation of dosing with VX-950, the authors report and all patients experienced decreases of at least 2-log10 from baseline.

Some patients in the 450-mg and 1250-mg groups experienced viral breakthrough between days 7 and 14, the researchers note, but viral HCV RNA levels continued to decrease through the entire dosing period in the 750-mg group.

Responses to VX-950 did not differ significantly between patients who had received prior treatment for HCV and those who were treatment na�ve, the report indicates. Moreover, there were no serious or severe adverse events, the investigators say, although patients receiving VX-950 were more likely than patients receiving placebo to report diarrhea, nausea, fatigue, and dry skin.

"VX-950 was effective in reducing viral load in a population in which 79% of patients had not responded to prior interferon-based regimens," the authors point out. Combination treatment with pegylated interferon-alfa and ribavirin, they add, "is effective in only approximately 50% of patients."

Dr. Reesink noted that "while these data are from early clinical studies, the degree of viral suppression observed is unprecedented and has led to well-justified optimism about the potential for VX-950 to lead a transformation in the treatment of HCV."

"VX-950 is now being evaluated in two large phase 2 studies involving genotype 1 patients," Dr. Reesink concluded. "In these studies, VX-950 is being dosed in combination with pegylated interferon both with and without ribavirin."

Gastroenterology 2006;131:997-1002.