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New HCV Drug NM283 + Peginterferon Study
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Reported by Jules Levin
Nezam Afdahl reported today Nov 1, 2004 in the late afternoon oral session at the 55th Annual AASLD liver meeting in Boston. Results from two studies of NM283, the new polymerase inhibitor for HCV. Patients were given doses ranging from 50 mg once daily to 400 once daily, 200 twice daily, 800 mg once daily. Some patients were titrated from 100 to 800 mg once daily. 80-100% of patients were IFN failures. Viral load was high 6.7 log HCV RNA. All patients were genotype 1 and non-cirrhotic.
The highest dose 800 mg QD showed a -1.2 log viral load reduction after 16 days of dosing. Of the 10 patients receiving this dose, 3 had <1 log reduction in viral load, 6 had reductions of 1-1.8 logs, and 1 patient had a 2.37 log reduction at the end of the 16 day dosing period. There were no serious adverse events or dose limiting toxicities. All 78 compliant patients completed treatment. 1 patient discontinued for non-compliance. There were no grade 3 or 4 lab abnormalities during treatment; no pattern of lab abnormalities. There were GI side effects, 'transient nausea, total of 12 patients with vomiting':
--seen primarily at doses >=400 mg/day
--30/36 (83%) nausea events rated "mild", 6/36 (17%) "moderate"
--most with onset within the first 7 days and duration <2 days
--12/31 (39%) of adverse events reported by placebo pts were GI in origin
NM283 + Peginterferon
NM283 and IFN-a show synergistic antiviral effect in BVDV model in vitro. 39 treatment-naïve patients received NM283+PegIFN. Patients had compensated chronic HCV, all genotype 1, HCV RNA >5 log, ALT <5 x ULN. Patients were randomized 2:3 to NM283 monotherapy (n=12) vs NM283 plus pegylated IFNa-2b (n=18):
pegIFN a-2b 1.0 ug/kg on days 8, 15, and 22
NM283: 400→600→800 mg QD to day 8 then 800 mg QD to day 28.
7 patients received 800 mg QD NM283 & 12 patients received 800 mg QD plus pegIFN. Baseline characteristics were similar for both groups: 6 log copies/ml viral load. Mean reduction in HCV RNA was -0,7 log at day 28 for patients receiving NM283 alone and -2.7 log copies/ml for patients receiving the combination. When looking at the individual 12 patient responses: -0.50, -0.90, -1.34, 4 patients had -2.19 to -2.65 log reductions, and 5 patients had -3.63 log to -4.55 log reductions at day 28. These last 9/12 patients had an Early Viral Response by week 4 after just 3 weekly injections of IFN, that is a >2 log reduction before 12 weeks.
This drug may offer improved efficacy outcomes especially for genotype 1 and previous nonresponders.
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