Protease Inhibitor Boceprevir Improves Response for Treatment-Naive and
Merck's investigational hepatitis C
virus (HCV) protease inhibitor boceprevir
improved sustained response rates when combined with pegylated
interferon plus ribavirin in both previously untreated patients
and those who were non-responders or relapsers after prior
therapy, according to 2 Phase 3 studies presented at the 18th
Conference on Retroviruses and Opportunistic Infections (CROI
2011) this month in Boston.
of direct-acting antiviral agents that interfere with various steps
of the HCV lifecycle will usher in a new era of treatment for chronic
hepatitis C. The current standard-of-care, pegylated
interferon (Pegasys or PegIntron) plus ribavirin, leads to sustained
virological response (SVR), or a cure, less than half the time for individuals
with hard-to-treat HCV genotype 1.
such drugs -- boceprevir and Vertex's HCV protease inhibitor telaprevir
-- are expected to be approved this year. Initially, they will be used
in combination with standard-of-case therapy, but all-oral regimens
without interferon are currently being studied.
researchers presented final data from 2 pivotal Phase 3 studies of telaprevir:
SPRINT-2, which enrolled previously untreated patients, and RESPOND-2,
which enrolled prior non-responders and relapsers. These results were
presented at the American Association for the Study of Liver Diseases
(AASLD) meeting this past fall.
and RESPOND-2 did not include people with HIV -- making these presentations
unusual for CROI -- but HIV specialists recognize the need to get up
to speed on hepatitis C treatment, since many HIV positive people are
coinfected with HCV. As recently
reported, the conference also featured the first data on telaprevir
for HIV/HCV coinfected individuals.
SPRINT-2 included 1097 treatment-naive HCV genotype 1 patients (about
60% men). Participants were divided into cohorts according to race,
as people of African descent do not respond as well to interferon-based
therapy. One cohort included 159 black patients, while the other included
938 people of other racial/ethnic groups ("non-black"). Most
had high HCV viral load and nearly 10% had advanced liver fibrosis.
started a regimen of 1.5 mcg/kg/week pegylated
interferon alfa-2b (PegIntron) plus 600-1400 mg/day weight-adjusted
ribavirin for a 4-week lead-in period. After this, they were randomly
assigned to continue on pegylated interferon/ribavirin, either alone
or in combination with 800 mg boceprevir 3-times-daily.
recipients were further allocated to receive either the triple combination
for a fixed duration of 48 total weeks or response-guided therapy. In
the latter arm, all participants stopped boceprevir at week 28. Those
with undetectable HCV RNA during weeks 8-24 stopped all drugs, while
those with continued detectable HCV viral load stayed on pegylated interferon/ribavirin
through week 48.
an intent-to-treat analysis, SVR rates were significantly higher
in the boceprevir arms -- 66% with fixed-duration treatment and
63% with response-guided therapy -- compared with the standard therapy
all arms, white patients had higher response rates than blacks:
68% vs 53% in the fixed duration boceprevir arm, 67% vs 42% in the
response-guided therapy arm, and 40% vs 23% in the standard therapy
relapse rate was 9% in both boceprevir arms, compared with 22% in
the standard therapy group.
Almost all boceprevir recipients with undetectable HCV RNA during
weeks 8-24 achieved SVR: 96% with fixed-duration boceprevir, 97%
with response-guided therapy.
boceprevir participants who had detectable HCV viral load at least
once during weeks 8-24, still 74% achieved SVR in both arms.
most common treatment-related adverse events across arms were fatigue,
headache, and nausea.
and dysgeusia (odd taste sensations) were more common in the boceprevir
groups than in the standard therapy group.
of discontinuation due to adverse events, however, were similar
across arms: 16% in the standard therapy arm, 16% in the boceprevir
fixed-duration arm, and 12% in the response-guided therapy arm.
these findings, the researchers concluded that a regimen of boceprevir
plus pegylated interferon/ribavirin "significantly increased SVR"
compared with standard therapy alone, and HCV RNA at week 8 could be
used to determine duration of pegylated interferon/ribavirin.
RESPOND-2 enrolled 400 treatment-experienced genotype 1 patients, both
prior non-responders and relapsers (undetectable at the end of treatment
followed by viral rebound). About two-thirds were men, 12% were black,
and 12% had liver cirrhosis.
participants initially received pegylated interferon/ribavirin standard
therapy for a 4-week lead-in period. They were then randomly assigned
to continue on pegylated interferon/ribavirin either alone or in combination
with 800 mg 3-times-daily boceprevir.
Boceprevir recipients were assigned to either stay on triple therapy
through week 48 or use response-guided therapy. In the latter group,
participants stopped boceprevir at week 36; those with undetectable
HCV RNA at week 8 stopped all treatment, while those with detectable
viral load continued on pegylated interferon/ribavirin through week
an intent-to-treat analysis, patients in the boceprevir arms had
significantly higher SVR rates -- 67% with fixed-duration therapy
and 59% with response-guided therapy -- than those in the standard
therapy arm (21%).
with undetectable HCV RNA at week 8 had high SVR rates in all arms:
88% with fixed-duration boceprevir, 86% with response-guided boceprevir,
and 100% with standard therapy.
taking boceprevir, however, were about 6 times more likely to have
undetectable HCV RNA at week 8 (46%-52% vs 9%).
In all arms, previous relapsers had higher SVR rates than prior
non-responders: 75% vs 52% with fixed-duration boceprevir, 40% vs
69% with response-guided boceprevir, and 29% vs 7% with standard
too, the most common adverse events were fatigue, headache, and
occurred about twice as often in the boceprevir arms: 46% with fixed-duration
boceprevir, 43% with response-guided boceprevir, and 20% with standard
adverse events likewise occurred about twice as often in the boceprevir
arms: 14%, 10%, and 5%, respectively.
concluded that boceprevir added to pegylated interferon/ribavirin "significantly
They added that boceprevir could be used to treat patients with all
types of interferon non-responsiveness, and that fixed-duration and
response-guided therapy were "equally effective."
Abstract 115: John Hopkins Univ School of Medicine, Baltimore, MD;
Cedars-Sinai Med Ctr, Los Angeles, CA; Gastroenterology/Hepatology/Certified
Endoscopy Ctrs, Alexandria, VA; St Louis Univ School of Medicine, St
Louis, MO; AO Fatebenefratelli e Oftalmico, Milan, Italy; Hannover Medical
School, Hannover, Germany; Ctr for the Study of Hepatitis C, Weill Cornell
Medical College, New York, NY; Univ of Pennsylvania, Philadelphia, PA;
Merck, Whitehouse Station, NJ; Ctr Hosp Univ de Nancy, Univ Henri Poincaré
Nancy 1, Vandoeuvre-lès-Nancy, France.
Abstract 116: Henry Ford Hosp, Detroit, MI; St Louis Univ School of
Medicine, St Louis, MO; Alamo Medical Research, San Antonio, TX; Univ
Paris, Hosp Beaujon, Clichy, France; Baylor College of Medicine, Houston,
TX; Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;
Cedars-Sinai Med Ctr, Los Angeles, CA; Merck, Whitehouse Station, NJ;
Hosp Univ Vall d'Hebrón, Barcelona, Spain.
F Poordad, J McCone, et al. BOC Combined with P/R for Treatment-naive
Patients with HCV Genotype-1: SPRINT-2 Final Results. 18th Conference
on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February
27-March 2, 2011. Abstract
B Bacon, E Lawitz, et al. HCV RESPOND-2 Final Results: High Sustained
Virologic Response among Genotype-1 Previous Non-responders and Relapsers
to pegIFN/RBV when Re-treated with BOC + PEGINTRON/RBV
18th Conference on Retroviruses and Opportunistic Infections (CROI 2011).
Boston. February 27-March 2, 2011. Abstract