BMS-790052
+ Pegylated Interferon/Ribavirin Works Well for First HCV Treatment
| SUMMARY:
About 90% of treatment-naive genotype 1 hepatitis C patients
achieved sustained response at 12 weeks post-treatment using
the experimental HCV protease inhibitor BMS-790052 plus
pegylated interferon/ribavirin, researchers reported at
EASL 2011. |
By
Liz Highleyman
People with chronic hepatitis
C Virus (HCV) infection undergoing treatment for the first
time have the greatest likelihood of achieving sustained virological
response (SVR), or continued undetectable HCV viral load after
completing therapy.
Nevertheless,
only about half of people with hard-to-treat HCV genotype 1
are cured the first time. New direct-acting antiviral drugs
that target various steps of the HCV lifecycle increase the
chances of treatment success when added to standard-of-care
therapy -- pegylated
interferon plus ribavirin -- and may shorten treatment duration.
In
a late-breaker poster presented at the European Association
for the Study of the Liver conference (EASL
2011) this month in Berlin, Stanislas Pol from Hôpital
Cochin in Paris and colleagues described a study looking at
3 doses of BMS-790052
combined with standard therapy.
This
Phase 2a trial included 48 genotype 1 chronic hepatitis C patients
undergoing treatment for the first time. About two-thirds were
men and the median age was about 50 years. About 80% were white,
two-thirds had HCV genotype 1a, and about one-third had the
favorable IL28B CC gene pattern (though this varied across study
arms).
Participants
were randomly assigned to received BMS-790052 at doses of 3
mg, 10 mg, or 60 mg once-daily in combination with pegylated
interferon alfa-2a (Pegasys) plus weight-based ribavirin, or
else standard therapy alone, all for 48 weeks.
Results
 |
In
an intent-to-treat analysis at 4 weeks, 42% of patients
taking BMS-790052 3 mg, 92% taking 10 mg, and 83% taking
60 mg achieved rapid virological response (RVR), compared
with 8% in the standard therapy control group. |
|
At
12 weeks, 42%, 83%, and 75% of patients, respectively, in
the 3 BMS-790052 dose arms still had undetectable viral
load, compared with 8% in the standard therapy arm. |
|
Sustained
virological response rates 12 weeks after completing therapy
(SVR12) were again 42% (5 of 12), 92% (11 of 12), and 83%
(10 of 12), respectively, in the BMS-790052 arms, while
the standard therapy arm rose to 25% (3 of 12). |
|
Participants
in the BMS-790052 10 mg and 60 mg arms had similar response
rates regardless of IL28B genotype. |
|
2 people experienced on-treatment HCV breakthrough or post-treatment
relapse in the BMS-790052 60 mg arm, compared with 3 in
the 10 mg arm, 7 in the 3 mg arm, and 9 in the standard
therapy arm. |
|
BMS-790052
was generally well-tolerated, with overall adverse event
rates similar to those seen with standard therapy. |
|
However,
treatment interruptions, drug discontinuations, and dose
reductions were more likely in the highest BMS-790052 dose
group. |
Based
on these findings, the researchers concluded, "BMS-790052
is a potent HCV replication complex inhibitor and can achieve
high rates of SVR at week 12 in HCV genotype 1-infected patients"
when combined with pegylated interferon/ribavirin.
Sustained
response rates were high with BMS-790052 at doses of 10 mg (92%)
or 60 mg (83%), they added, but the lowest dose was not as effective.
Another
study presented at the conference showed that BMS-790052
plus a second direct-acting drug, BMS-650032, cured most prior
non-responders when used in a quadruple regimen with pegylated
interferon/ribavirin, and nearly 40% when the 2 oral drugs were
used alone.
Investigator affiliations: Hôpital Cochin, Paris, France;
Liver Institute at Methodist Health System, Dallas, TX; Metropolitan
Research, Fairfax, VA; The Research Institute, Springfield,
MA; University of Colorado, Aurora, CO; Options Health Research,
LLC, Tulsa, OK; CHU Henri Mondor, Creteil, France; Yale University
School of Medicine, New Haven, CT; Hopitale Adultes de Braboios,
Vandoeuvre les Nancy, France; Alabama Liver & Digestive
Specialists, Montgomery, AL; James J Peters VAMC, Bronx, NY;
Healthcare Research Consultants, Tulsa, OK; Mercy Medical Center,
Baltimore, MD; Carolinas Center for Liver Disease Research Dept,
Statesville, NC; Bristol Meyer Squibb Co., Wallingford, CT.
4/12/11
Reference
S
Pol. RH Ghalib, VK Rustgi, et al. First report of SVR12 for
a NS5A replication complex inhibitor, BMS-790052 in combination
with peg-IFN-alfa-2a and RBV: phase 2a trial in treatment-naive
HCV-genotype 1 subjects. 46th Annual Meeting of the European
Association for the Study of the Liver (EASL 2011). Berlin.
March 30-April 3. Abstract
2.
Other
Source
Bristol-Myers
Squibb Company. Investigational Direct-Acting Antiviral BMS-790052
Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained
Virologic Response in Phase II Dose-Ranging Study of Treatment-Naive
Hepatitis C Patients. Press release. March 31, 2011.
