BMS-790052/BMS-650032
Combo Cures Hepatitis C without Interferon
| SUMMARY:
Most prior non-responders with HCV genotype 1 achieved sustained
response with a quadruple combination containing 2 experimental
agents plus pegylated interferon/ribavirin, and nearly 40%
did so using only the 2 oral drugs -- BMS-790052 and BMS-650032
-- researchers reported at EASL 2011. |
By
Matt Sharp
In one of the most exciting studies presented at the European
Association for the Study of the Liver conference (EASL
2011) this month in Berlin, 2 new oral agents in combination
with standard-of-care
hepatitis C treatment showed remarkable results in people
with chronic hepatitis C who
had not responded to prior standard treatment.
Even
more impressive, 4 of 11 patients treated with the 2 oral drugs
alone achieved sustained response, offering proof of concept
for what doctors and people with hepatitis C virus (HCV) have
hoped for a long time: a cure for hepatitis C without the toxic
regimen of pegylated
interferon/ribavirin.
For
a little background, only about 40% of people with difficult-to-treat
HCV genotype 1 achieve a sustained virological response (SVR,
or a cure) after 48 weeks of pegylated interferon/ribavirin
alone. Those who do not respond to a first course of standard-of-care
therapy (non-responders) typically do not do well when retreated
again with the same regimen. The lowest cure rates are seen
in prior null responders, those who do not suppress HCV RNA
by at least 2 log IU/mL after 12 weeks of therapy.
The
current crop of new direct-acting antiviral drugs are showing
more promise for all populations of people with HCV. So far
most of these drugs have been added to pegylated interferon/ribavirin,
but some are now being tested in all-oral combinations, allowing
people with HCV to avoid the side effects of interferon and
ribavirin.
In
a study presented in Berlin, Anna Lok and colleagues looked
at 2 of these direct-acting agents that are thought to be synergistic:
BMS-790052,
a first-in-class NS5A replication complex inhibitor, and BMS-650032,
an HCV protease inhibitor.
The
Phase 2a trial, which included 21 genotype 1 null responders,
compared 2 arms, one using only 60 mg once-daily BMS-790052
plus 600 mg twice-daily BMS-650032 (Group A) and the second
using the 2 new drugs in combination with 180 mcg/week pegylated
interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted
ribavirin (Group B), all for 24 weeks.
About
80% of participants in Group A and 40% in Group B were men.
Most were white and the median age was about 55 years. About
90% had the unfavorable CT or TT IL28B gene patterns, which
predicts poor response to interferon.
Results
were striking especially in the group using the 2 new drugs
without standard-of-care therapy. In Group A, 4 of 11 participants
(36%) reached SVR at 12 and 24 weeks. As a result, these data
show that HCV infection can be cured without interferon and
ribavirin.
In
the group randomized to receive quadruple therapy, 10 of 10,
or 100%, reached SVR at 12 weeks, and 9 of 10 (90%) did so at
24 weeks -- a high cure rate in this difficult-to-treat population.
The person who had SVR at 12 but not 24 weeks again showed HCV
RNA below the limit of quantification when tested 35 days later.
Resistance
to both BMS-790052 and BMS-650032 was seen in the 6 people who
had HCV breakthrough. Most adverse events, including fatigue,
neutropenia, and ALT elevations, were moderate, and there were
no serious adverse events or discontinuations due to adverse
events in either group.
Taken
together, these results show that BMS-790052 and BMS-650032
are powerful new agents that could change the course of how
HCV is treated in the near future.
Another
study presented at the conference showed that BMS-790052
plus pegylated interferon/ribavirin was highly effective for
people with HCV genotype 1 starting treatment for the first
time.
Investigator Affiliations: Medicine, University of Michigan,
Ann Arbor, MI; Bristol-Myers Squibb Research and Development,
Hopewell, NJ; Alamo Medical Research, San Antonio, TX; The Research
Institute, Springfield, MA; University of Colorado-Denver, Aurora,
CO; The Liver Institute at Methodist Dallas, Dallas, TX; Carolinas
Center for Liver Disease Research Dept, Statesville, NC; Metropolitan
Research, Fairfax, VA; Bristol-Myers Squibb Research and Development,
Wallingford, CT; Bristol-Myers Squibb Research and Development,
Princeton, NJ.
4/12/11
Reference
A Lok, D Gardiner, E Lawitz, et al. Quadruple Therapy with BMS-790052,
BMS-650032 and PEG-IFN/RBV for 24 Weeks; Results in 100% SVR12
in HCV Genotype 1 Null Responders. 46th Annual Meeting of the
European Association for the Study of the Liver (EASL 2011).
Berlin. March 30-April 3. Abstract
418.
Other Source
EASL.
Quadruple Therapy Shows 100% Sustained Virological Response
(SVR) for HCV Patients Previously Unresponsive to Treatment.
Press release. April 2, 2011.
