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ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.
In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.
The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.
The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.
A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.
In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.
The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.
The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.
One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.
Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.
The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.
The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.
ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.
In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.
The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.
The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.
A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.
In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.
The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.
The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.
One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.
Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.
The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.
The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.
ORLANDO – An investigational pegylated formulation of subcutaneous interferon beta-1a appears to offer the efficacy and safety of currently available interferon therapy for relapsing-remitting multiple sclerosis with the advantage of less frequent injections, a study has shown.
In the phase III, double-blind ADVANCE trial, peginterferon beta-1a at 125 mcg self-administered subcutaneously every 2 weeks for 1 year consistently provided statistically significant advantages over placebo for all clinical and radiologic outcomes, Dr. Peter A. Calabresi reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Peginterferon beta-1a dosed every 4 weeks was less effective than every 2 weeks. It bested placebo on some but not all endpoints, added Dr. Calabresi, professor of neurology and director of the multiple sclerosis center at Johns Hopkins University, Baltimore.
The ADVANCE trial involved 1,516 randomized patients with relapsing-remitting MS, 86% of whom had a baseline Expanded Disability Status Scale (EDSS) score of less than 4.
The primary endpoint was the annualized relapse rate at 1 year: 0.397 with placebo; 0.2888 with peginterferon beta-1a every 4 weeks, for a 27.5% reduction compared with placebo; and 0.256 with biweekly therapy, for a 35.6% reduction. The 1-year incidence of relapse was reduced by 26% with monthly dosing and by 39% with biweekly dosing of peginterferon beta-1a, compared with placebo.
A key secondary outcome measure, disability progression during year 1 as defined by at least a 1-point increase in the EDSS sustained for 12 weeks or more, was reduced by 38% in both peginterferon beta-1a arms, compared with placebo.
In terms of MRI outcomes reflecting disease activity, the mean number of new or enlarging T2 lesions at 1 year was 10.9 with placebo, 7.9 with peginterferon every 4 weeks, and 3.6 – a 67% reduction compared with placebo – with biweekly therapy. The mean number of gadolinium-enhancing MRI lesions was 1.4 with placebo, 0.9 with peginterferon every 4 weeks, and 0.2 with biweekly peginterferon, an 86% reduction compared with placebo.
The incidence of interferon-neutralizing antibodies believed capable of interfering with the effect of the drug was reassuringly low at less than 1% in all three study arms at 1 year.
The adverse events profile of peginterferon beta-1a would be familiar to physicians who prescribe other interferons: injection site reactions, flulike illness, and headaches, for example – all typically rated mild and lasting less than 48 hours, Dr. Calabresi continued.
One audience member, noting that peginterferon beta-1a every 2 weeks was clearly more effective than every 4 weeks, asked why once-weekly injections weren’t studied. Dr. Calabresi replied that the every-2-week regimen appears to provide a reduction in the relapse rate that’s roughly equivalent to that achieved with standard nonpegylated interferon beta-1a given more frequently. For patients who’ve done well on interferon therapy for years, the idea of switching from Avonex given intramuscularly once weekly or Rebif given subcutaneously three times per week to an every 2-week dosing regimen that provides the efficacy and safety they’re accustomed to is likely to be very attractive, he added.
Pegylation is a strategy for increasing the half-life and pharmacodynamic effects of a drug. Less frequent dosing means greater convenience for patients and possibly improved adherence as well. Ninety-one percent of the placebo group completed year 1 of ADVANCE, as did 88% on peginterferon beta-1a given every 4 weeks and 86% on biweekly dosing.
The ADVANCE study is now in its second and final year, during which patients continue on the same peginterferon dosing schedule they had in year 1, while patients formerly on placebo are randomized to a year on one of the two peginterferon dosing regimens. After the 2 years of ADVANCE are completed, there will be a 2-year extension study called ATTAIN.
The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.
AT THE CMSC/ACTRIMS ANNUAL MEETING
Major Finding: Patients on investigational pegylated interferon beta-1a self-administered by subcutaneous injection once every 2 weeks had an annualized relapse rate at 1 year of 0.256, a 35.6% reduction compared with placebo. Injections once every 4 weeks resulted in an annualized relapse rate at 1 year of 0.2888.
Data Source: A phase III, double-blind, multicenter clinical trial (ADVANCE) including 1,516 patients with relapsing-remitting MS randomized to 1 year of placebo or subcutaneous pegylated interferon beta-1a at 125 mcg self-administered either every 2 weeks or every 4 weeks.
Disclosures: The ADVANCE trial is sponsored by Biogen Idec. Dr. Calabresi reported receiving grant support from that company and serving as a consultant to Vaccinex, Abbott, and Vertex.
