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

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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.

Klein

Office of Special Health Issues

Food and Drug Administration

Division of Antiviral Products

Food and Drug Administration

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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.

Klein

Office of Special Health Issues

Food and Drug Administration

Division of Antiviral Products

Food and Drug Administration