Dose Escalation Trial Assesses Tolerance, Pharmacokinetics, and Antiviral Activity of NM 283, a Novel Antiviral Treatment for Hepatitis C

Current therapy for hepatitis C has adverse side effects and induces a sustained virologic response in less than half of patients infected with hepatitis C virus (HCV) genotype 1, the most common genotype (60-70% of patients) in the USA, Europe and Japan.

NM 283, a novel candidate HCV RNA polymerase inhibitor, has anti-flavivirus activity that is highly synergistic with interferon alfa in vitro, and suppresses viremia in chimpanzees chronically infected with human-derived HCV-1 (Standring, EASL 2003).

In this presentation at DDW 2004 in New Orleans, researchers reported on the first clinical data for NM 283 in humans.

A phase I/II dose escalation trial is investigating NM 283 in the range 50-800 mg/day. Subjects are treatment-naïve or experienced adults with HCV-1 associated chronic hepatitis C, with baseline serum HCV RNA >5 log10.

For each dose, 12-patient cohorts are randomized 10:2 to receive NM283 or placebo for 15 days with 14 days of follow-up.

Results

Dosing cohorts of 50, 100, 200, and 400 mg/day, involving 48 patients, have been completed with once-daily oral dosing. Dose-related decreases in serum HCV RNA at Day 16 were observed, ranging from a mean 0.15 log10 at the lowest dose (50 mg/day) to 0.73 log10 at 400 mg/day, which is about half of the anticipated clinical dose.

Tolerance of study treatment has been satisfactory, with no serious adverse events, dose-limiting toxicities, or pattern of laboratory abnormalities. At 400 mg/day, some NM2 83-treated patients experienced transient mild nausea (5/10) or vomiting (2/10) on Day 1, but all patients completed treatment without modification.

NM283 is well absorbed, with dose-proportional plasma exposure.

The authors conclude, “NM 283 exhibits consistent antiviral activity with satisfactory tolerance and linear pharmacokinetics in HCV-1 infected chronic hepatitis C patients. Expanded testing of NM283, alone and in combination with peg-interferon, is anticipated.”

05/24/04

Reference
E Godofsky and others. Phase I/II Dose Escalation Trial Assessing Tolerance, Pharmacokinetics, and Antiviral Activity of NM283, a Novel Antiviral Treatment for Hepatitis C. Abstract 407 (plenary). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.