FDA Approves Pegasys & Copegus for Children between 5 years & 17 years
On August 22, 2011, the FDA approved the combination of Pegasys and Copegus
for the treatment of chronic hepatitis C virus (HCV) infection in pediatric
patients 5 through 17 years of age with chronic hepatitis C (CHC) virus
infection who have compensated liver disease and have not been previously
treated with interferon alpha.. Pegasys/Copegus combination treatment for
HCV in adults was approved in December, 2002, and that original approval
included a postmarketing requirement to evaluate the drugs in pediatric
patients.
Hoffmann-La Roche Inc submitted the results of Study NV17424 to support the
use of Pegasys/Copegus in pediatric patients. Subjects participating in the
study received Pegasys at a dose of BSA x 180 mcg/1.73 m2 once weekly plus
Copegus at a dose of approximately 15 mg/kg/day in two divided doses. Study
participants received 24 weeks of blinded treatment and were determined to
be responding or not responding based on undetectable HCV RNA (< 50 IU/mL).
Responders continued their assigned treatment to 48 weeks regardless of HCV
genotype. Nonresponders were unblinded and either stopped treatment (if they
were in the Pegasys/Copegus group) or rolled into a "compassionate"
Pegasys/Copegus combination group to continue 48 weeks of treatment (if they
were in the Pegasys/placebo group). Subjects were followed off-treatment for
an additional 24 weeks after the completion of 48 weeks of treatment to
assess the primary efficacy endpoint, the proportion of subjects achieving
sustained virologic response (SVR), defined as undetectable HCV RNA at 24
weeks post-treatment. Any subject switching from randomized Pegasys/placebo
to the compassionate combination Pegasys/Copegus was counted as a treatment
failure.
The trial enrolled 114 previously untreated pediatric subjects 5 through 17
years of age (of whom 55% were less than 12 years old who were randomized to
receive either combination treatment of Pegasys/Copegus or Pegasys/placebo.
The initial randomized arms were balanced for demographic factors: 55
subjects received initial combination treatment of Pegasys/Copegus and 59
received Pegasys/placebo. In the overall study population, 45% were female,
80% were Caucasian, and 81% were infected with HCV genotype 1. As previously
shown in adults, the combination of Pegasys/Copegus provided significantly
better response rates as measured by SVR compared to treatment with Pegasys
alone. The SVR rate for study subjects receiving Pegasys/Copegus was 53%
(29/55) compared to 20% (12/59) in the group receiving Pegasys. Subjects
with the more difficult to treat genotype 1 receiving Pegasys/Copegus
demonstrated SVR of 47% (21/45) while the smaller subgroup with non-genotype
1 had higher SVR (80%, 8/10).
The safety profile of Pegasys with or without Copegus in pediatric subjects
in the clinical trial was similar to that observed in adults receiving
similar treatment. Seven subjects receiving combination Pegasys/Copegus
treatment for 48 weeks discontinued therapy for safety reasons (depression,
psychiatric evaluation abnormal, transient blindness, retinal exudates,
hyperglycemia, type 1 diabetes mellitus, and anemia). Dose modifications
because of adverse events and laboratory abnormalities occurred commonly in
the pediatric trial, about 35% during the randomized treatment period in
both arms. The most common reason for modification of Pegasys was
neutropenia and the most common reason for dose reduction of Copegus was
anemia. The most common non-serious treatment related adverse events
reported among subjects receiving Pegasys/Copegus included influenza-like
illness (91 %), headache (62%), gastrointestinal disorders (56%), injection
site reactions (45%), irritability (31%), fatigue (27%), rash (20%),
pruritis (15%), and insomnia and decreased appetite (13% each).
The most important pediatric-specific safety issue related to
Pegasys/Copegus was growth delay. Pediatric subjects treated with
Pegasys/Copegus combination therapy experienced a delay in gaining weight
and height after 48 weeks of therapy compared with baseline. Both weight and
height for age z-scores as well as the percentiles of the normative
population for subject weight and height decreased during treatment. At the
end of 2 years follow-up after treatment, most subjects had returned to
baseline normative growth curve percentiles for weight and height. At 2
years post-treatment, 16% of subjects remained 15 percentiles or more below
their baseline weight curve and 11% remained 15 percentiles or more below
their baseline height curve.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Linda Lewis
Division of Antiviral Products
Food and Drug Administration