Telaprevir plus Pegylated Interferon and Ribavirin Produces Rapid Response and
Is Well Tolerated in 28-day Study By
Liz Highleyman Given
the limited efficacy and difficult side effects of interferon-based
therapy for chronic hepatitis C virus (HCV)
infection, researchers are studying a variety of oral antiviral agents that
directly target different steps of the viral lifecycle. One of the most promising
is telaprevir
(previously known as VX-950), an experimental HCV NS34A protease inhibitor
being developed by Vertex Pharmaceuticals and Tibotec.
As reported in
the August 2008 Journal of Hepatology, Eric Lawitz and colleagues conducted
a small trial to assess the safety and antiviral activity of telaprevir added
to standard combination therapy for chronic hepatitis C.
The study included
12 treatment-naive patients with chronic genotype
1 HCV infection. All received 750 mg telaprevir every 8 hours plus 180 mcg/week
pegylated
interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-based ribavirin for
28 days. At the discretion of the investigator and patient, participants could
then commence off-study treatment with Pegasys plus ribavirin without telaprevir
for up to 44 weeks (for a total of 48 weeks, the standard duration of therapy
for genotype 1).
Results
•
The combination of telaprevir, pegylated interferon, and ribavirin was well tolerated,
with no serious adverse events or treatment discontinuations.
•
Rash or pruritus (itching) occurred in 5 of the 12 patients; all cases resolved
either during or after completion of telaprevir treatment.
•
All 12 patients experienced rapid viral response (RVR), or undetectable HCV RNA
levels by day 28.
•
8 of the participants underwent 44 weeks of off-study pegylated interferon plus
ribavirin after finishing the telaprevir phase.
•
All 8 achieved sustained viral response (SVR), or undetectable HCV RNA 24 weeks
after completion of therapy.
•
1 individual who received only 22 weeks of treatment achieved SVR.
In
conclusion, the study authors wrote, "The combination of telaprevir, peginterferon
alfa-2a, and ribavirin was generally well tolerated. Events of pruritus and rash
resolved during or after end of telaprevir dosing. All 12 patients achieved an
RVR."
While this is one of the first studies of telaprevir to be published
in a peer-reviewed journal, data from the larger and longer PROVE-1,
PROVE-2, and PROVE-3
trials have been reported at recent scientific meetings.
A majority
of experts expect that directly targeted anti-HCV agents such as telaprevir will
have to be used in combination with interferon for the foreseeable future, but
addition of the new agents may
allow for shorter therapy.
Alamo Medical Research, San Antonio,
TX; Fundacion de Investigacion de Diego San Juan, Puerto Rico; Duke Clinical Research
Institute, Duke University, Durham, NC; Vertex Pharmaceuticals Incorporated, Cambridge,
MA.
7/22/08
References E
Lawitz, M Rodriguez-Torres, AJ Muir, and others. Antiviral effects and safety
of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C
patients. Journal of Hepatology 49(2): 163-169. August 2008. (Abstract) S
Zeuzem. Telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in chronic
hepatitis C patients. Journal of Hepatology 49(2): 157-159. August 2008. |
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