Response Data for Polymerase Inhibitor Mericitabine
76% of treatment-naive genotype 1 or 4 hepatitis C patients
achieved 12-week sustained response to mericitabine (formerly
RG7128) plus pegylated interferon/ribavirin, according to
a report at EASL 2011.
C virus (HCV) protease inhibitors will be the first direct-acting
antivirals to emerge from the development pipeline, but polymerase
inhibitors are not far behind. Mericitabine is a nucleoside
analog NS5B RNA-dependent RNA polymerase inhibitor being developed
by Roche/Genentech. The drug works by disabling an enzyme required
to copy HCV RNA. Preclinical studies indicated that it has a
high barrier to drug resistance.
Pockros from the Scripps Clinic and colleagues designed the
JUMP-C study to compare a response-guided therapy regimen of
mericitabine plus pegylated interferon alfa-2a (Pegasys) and
ribavirin versus standard therapy with pegylated
Phase 2b trial included 166 previously untreated chronic hepatitis
C patients with hard-to-treat HCV genotypes 1 or 4. About 60%
were men, 78% were white, 12% were black, and the average age
was 50 years. About 60% had HCV genotype 1a, 30% had 1b, and
6% had genotype 4. About one-quarter had advanced liver fibrosis
or cirrhosis (Metavir stages F3-F4).
were first randomly assigned to receive the mericitabine combination
or standard therapy. Within the former group, those who experienced
extended rapid virological response (eRVR, or HCV RNA < 15
IU/mL from week 4 to 22) received 1000 mg twice-daily mericitabine
plus standard doses of pegylated interferon and ribavirin for
24 weeks. Those who did not achieve eRVR received 24 weeks of
mericitabine triple therapy followed by a further 24 weeks of
pegylated interferon/ribavirin alone. Everyone in the standard
therapy control group received only pegylated interferon/ribavirin
for 48 weeks.
week 4, 63% of patients receiving mericitabine triple therapy
achieved RVR, compared with just 14% in the standard therapy
week 12, 89% of those taking mericitabine and 51% of those
on standard therapy achieved early virological response.
week 24, 91% of mericitabine recipients and 62% of standard
therapy recipients had undetectable HCV RNA.
of participants in the mericitabine group had extended RVR
were eligible to stop treatment at 24 weeks:
of these patients still had undetectable HCV viral
load 12 weeks after the end of treatment (sustained
virological response or SVR-12);
experienced viral relapse by 12 weeks post-treatment.
therapy recipients who did not achieve extended RVR and
patients in the standard therapy arm continued treatment;
overall, 56% had undetectable HCV RNA at week 36, but treatment
assignment remained blinded.
rates for mericitabine recipients who stopped treatment
at 24 weeks were similar regardless of IL28B gene pattern:
or TT (unfavorable): 72%.
and tolerability of mericitabine triple therapy were comparable
to standard therapy.
side effects were significantly more or less common in the
cell deficiencies and signs of impaired kidney function
were uncommon in both groups.
resistance-associated variants were observed among mericitabine
this interim analysis, mericitabine plus [pegylated interferon/ribavirin]
for 24 weeks was associated with very high rates of virological
suppression (91%) and high SVR-12 (76%) in patients with eRVR
(60%)," the researchers stated.
added that mericitabine appeared to overcome the disadvantage
of having an unfavorable IL28B gene pattern.
good safety and tolerability profile, strong antiviral potency
and no evidence of resistance-related breakthrough makes mericitabine
highly desirable for further study, including combinations with
other [directing-acting antivirals]," they concluded.
Scripps Clinic Research Center, La Jolla, CA; Center for Liver
Diseases, University of Chicago Hospitals, Chicago, IL; Hawaii
Medical Center, Honolulu, HI; University of Kansas Hospital
Medical Center, Kansas City, KS; Division of Gastroenterology,
University of British Columbia, Vancouver, BC, Canada; Ottawa
Hospital, Ottowa, ON, Canada; Dartmouth-Hitchcock Medical Center,
Lebanon, NH; Infections Limited Hawaii, Honolulu, HI; Roche,
Nutley, NJ; Genentech, South San Francisco, CA; Baylor College
of Medicine, Houston, TX.
The JUMP-C study was funded by Roche.
P Pockros, D Jensen, N Tsai, et al. First SVR data with the
nucleoside analogue polymerase inhibitor mericitabine (RG7128)
combined with peginterferon/ribavirin in treatment-naive HCV
G1/4 patients: interim analysis from the JUMP-C trial. 46th
Annual Meeting of the European Association for the Study of
the Liver (EASL 2011). Berlin. March 30-April 3. Abstract