The
new oral HCV protease inhibitor telaprevir
(VX-950) generated considerable interest at the 57th American Association
for the Study of Liver Diseases (AALSD) meeting held last month in Boston. As
previously reported, studies to date have shown that telaprevir is well-tolerated
and suppresses HCV replication when used as monotherapy or in combination with
pegylated interferon.
In the first poster, M. Rodriquez-Torres
and colleagues presented data from an ongoing study designed to assess the safety
of telaprevir when given in combination with Pegasys plus ribavirin. Trial VX05-950-102
included 12 treatment-naive subjects with genotype 1 HCV. All received telaprevir
(750 mg three times daily) plus Pegasys (180 mcg weekly) plus ribavirin (1000-1200
mg daily) for 28 days. Then, patients stopped telaprevir and continued on standard
therapy.
Results
The 3-drug telaprevir/Pegasys/ribavirin combination was well tolerated over 28
days, with no serious adverse events.
The adverse event profile was consistent with that commonly seen among patients
taking Pegasys/ribavirin without telaprevir.
All subjects demonstrated a response to the study drug regimen, with 2 subjects
reaching undetectable HCV RNA levels (< 10 IU/mL) within 8 days of the start
of dosing.
All participants had undetectable HCV viral load at the end of the 28-day dosing
period.
All patients showed continued viral load decreases throughout the dosing period;
none experienced virological breakthrough.
Genetic sequencing revealed resistant viral variants in 2 subjects soon after
dosing began, but both achieved undetectable viral loads by Day 22.
After 12 weeks of follow-up on standard therapy (after discontinuing telaprevir),
11 participants had undetectable HCV RNA.
After 24 weeks, 9 subjects had maintained undetectable HCV RNA, 2 had detectable
viral load, and 1 was lost to follow-up.
In
conclusion, the researchers wrote, "Telaprevir/pegylated interferon/ribavirin
was well tolerated for 28 days in patients with HCV genotype 1. A rapid and substantial
antiviral effect of telaprevir was observed, with all subjects achieving undetectable
plasma HCV RNA within 28 days of dosing."
In the 2 patients with virological
breakthrough, genetic sequencing revealed both wild-type virus and the R155K mutation,
leading the researchers to suggest that breakthrough may be related to a poor
response to pegylated interferon/ribavirin, which would allow continued HCV replication. 14-Day
Study Follow-up
AT
AASLD, these researchers presented follow-up data from 20 participants in study
VX04-950-103 who initially received telaprevir, with or without Pegasys, for 14
days, then stopped telaprevir and continued on standard therapy with Pegasys plus
ribavirin. Results
At the end of 14 days of telaprevir monotherapy, the median HCV RNA decrease was
4.0 logs and 1 of 8 subjects had undetectable viral load (< 10 IU/mL).
Among patients receiving telaprevir plus Pegasys for 14 days, the median HCV RNA
decrease was 5.5 logs, and 6 of 8 subjects achieved undetectable viral load.
19 participants were followed on standard therapy through Week 24 (1 declined
further treatment).
At Week 24 (12 weeks after stopping telaprevir), all patients initially randomized
to the telaprevir/Pegasys groups who continued on Pegasys/ribavirin maintained
undetectable HCV RNA.
10 patients decided, in consultation with their physicians, to discontinue Pegasys/ribavirin
at 24 weeks: - 4 in the initial telaprevir monotherapy arm; - 6 in the initial
telaprevir/Pegasys combination arm.
During follow-up on standard therapy, there were no unusual adverse events not
normally seen with pegylated interferon/ribavirin.
"The
clinical data continue to demonstrate the substantial antiviral effects of telaprevir
monotherapy and the increased antiviral effects of telaprevir in combination with
pegylated interferon," the researchers concluded.
Summary
Conclusion
Taken
together, these results indicate that short-term use of telaprevir does not compromise
the efficacy of subsequent standard therapy with pegylated interferon plus ribavirin.
In addition, there was no evidence of adverse events related to prior use of telaprevir. Telaprevir
is currently being studied in longer Phase IIb trials (PROVE 1 in the U.S. and
PROVE 2 in Europe).
Fundación de Investigación de Diego,
Santurce, Puerto Rico; Ponce School of Medicine, Ponce, Puerto Rico; Alamo Medical
Research, San Antonio, TX; Duke Clinical Research Institute, Durham, NC; Vertex
Pharmaceuticals Inc., Cambridge, MA. Saarland University Hospital, Homburg/Saar,
Germany; Academic Medical Center, Amsterdam, Netherlands; Vertex Pharmaceuticals
Inc., Cambridge, MA.
12/01/06
References
M.
Rodriguez-Torres, E Lawitz, A Muir, and others. Current status of subjects receiving
peg-interferon-alfa-2a (Peg-IFN) and Ribavirin (RBV) follow-on therapy after 28-day
treatment with the hepatitis C protease inhibitor telaprevir (VX-950), Peg-IFN
and RBV. 57th AASLD. October 27-31, 2006. Boston, MA. Abstract 927.
N
Forestier, C J Weegink, S Purdy, and others. Current status of subjects receiving
peg-interferon-alfa-2a (Peg-IFN) and ribavirin (RBV) after a 14-day study of the
hepatitis C protease inhibitor telaprevir (VX-950), with Peg-IFN. 57th AASLD.
October 27-31, 2006. Boston, MA. Abstract 1142.
The 3-drug telaprevir/Pegasys/ribavirin combination was well tolerated over 28
days, with no serious adverse events. 
